Diagnosis is typically based on symptoms. Conditions that may result in similar symptoms include testicular torsion, inguinal hernia, and testicular cancer. Ultrasound can be useful if the diagnosis is unclear.

Epididymitis usually has a gradual onset. Typical findings are redness, warmth and swelling of the scrotum, with tenderness behind the testicle, away from the middle (this is the normal position of the epididymis relative to the testicle). The cremasteric reflex (elevation of the testicle in response to stroking the upper inner thigh) remains normal. This is a useful sign to distinguish it from testicular torsion. If there is pain relieved by elevation of the testicle, this is called Prehn's sign, which is, however, non-specific and is not useful for diagnosis.

Before the advent of sophisticated medical imaging techniques, surgical exploration was the standard of care. Today, Doppler ultrasound is a common test: it can demonstrate areas of blood flow and can distinguish clearly between epididymitis and torsion. However, inasmuch as torsion and other sources of testicular pain can consistently be determined by palpation alone, some studies have suggested that the only real benefit of an ultrasound, which is a fairly expensive procedure (~US$300 to US$800 in 2013), is to assure the patient that he does not have testicular cancer. Nuclear testicular blood flow testing is rarely used.

Additional tests may be necessary to identify underlying causes. In younger children, a urinary tract anomaly is frequently found. In sexually active men, tests for sexually transmitted diseases may be done. These may include microscopy and culture of a first void urine sample, Gram stain and culture of fluid or a swab from the urethra, nucleic acid amplification tests (to amplify and detect microbial DNA or other nucleic acids) or tests for syphilis and HIV.

Epididymitis can be classified as acute, subacute, and chronic, depending on the duration of symptoms.

Useful tests that may help in the determination of the cause include a urinalysis (usually normal in testicular torsion). Pyuria and bacteriuria (white blood cells and bacteria in the urine) in patients with acute scrotum suggests an infectious cause such as epididymitis or orchitis and specific testing for gonorrhea and chlamydia should be done. All people with chronic pain should be tested for gonorrhea and chlamydia.

In the United Kingdom, NGU is more often called non-specific urethritis; "" is a medical term meaning "specific cause has not been identified", and in this case refers to the detection of urethritis, and the testing for but found negative of gonorrhea. In this sense, the most likely cause of NSU is a chlamydia infection.

However, the term NSU is sometimes distinguished and used to mean that both gonorrhea and chlamydia have been ruled out. Thus, depending on the sense, chlamydia can either be the most likely cause or have been ruled out, and frequently detected organisms are "Ureaplasma urealyticum" and "Mycoplasma hominis".

Ultrasound is useful if the cause is not certain based on the above measures. If the diagnosis of torsion is certain, imaging should not delay definitive management such as physical maneuvers and surgery.

One study has proposed that elevated levels of soluble urokinase-type plasminogen activator receptor (SuPAR) in seminal plasma might be useful as a marker for MAGI.

MAGI can be diagnosed when there are two or more factors present that meet criteria defined by the World Health Organization (WHO):

It has been easy to test for the presence of gonorrhea by viewing a Gram stain of the urethral discharge under a microscope: The causative organism is distinctive in appearance; however, this works only with men because other non-pathogenic gram-negative microbes are present as normal flora of the vagina in women. Thus, one of the major causes of urethritis can be identified (in men) by a simple common test, and the distinction between gonococcal and non-gonococcal urethritis arose for this reason.

Non-gonococcal urethritis (NGU) is diagnosed if a person with urethritis has no signs of gonorrhea bacteria on laboratory tests. The most frequent cause of NGU (23%-55% of cases) is "C. trachomatis".

In most cases where orchitis is caused by epididymitis, treatment is an oral antibiotic such as cefalexin or ciprofloxacin until infection clears up. In both causes non-steroidal anti-inflammatory drugs such as naproxen or ibuprofen are recommended to relieve pain. Sometimes stronger pain medications in the opiate category are called for and are frequently prescribed by experienced emergency room physicians.

Orchitis is not rare in bulls and rams.

It has also been described in roosters.

Urinary catheters should be inserted using aseptic technique and sterile equipment (including sterile gloves, drape, sponges, antiseptic and sterile solution), particularly in an acute care setting. Hands should be washed before and after catheter insertion. Overall, catheter use should be minimized in all patients, particularly those at higher risk of CAUTI and mortality (e.g. the elderly or those with impaired immunity).

Spermatoceles can be discovered as incidental scrotal masses found on physical examination by a physician. They may also be discovered by self-inspection of the scrotum and testicles.

Finding a painless, cystic mass at the head of the epididymis, that transilluminates and can be clearly differentiated from the testicle, is generally sufficient. If uncertainty exists, ultrasonography of the scrotum can confirm if it is spermatocele.

If an individual finds what he suspects to be a spermatocele, he is advised to consult a urologist.

Treatment depends on the proximate cause. In one study, it was reported that 9 of 13 men who underwent vasectomy reversal in an attempt to relieve post-vasectomy pain syndrome became pain-free, though the followup was only one month in some cases. Another study found that 24 of 32 men had relief after vasectomy reversal.

Nerve entrapment is treated with surgery to free the nerve from the scar tissue, or to cut the nerve. One study reported that denervation of the spermatic cord provided complete relief at the first follow-up visit in 13 of 17 cases, and that the other four patients reported improvement. As nerves may regrow, long-term studies are needed.

One study found that epididymectomy provided relief for 50% of patients with post-vasectomy pain syndrome.

Orchiectomy is recommended usually only after other surgeries have failed.

A retrospective postal survey of 396 men found that 4% had significant genital pain for more than one year that required surgical intervention.

Another study contacted 470 vasectomy patients and received 182 responses, finding that 18.7% of respondents experienced chronic genital pain with 2.2% of respondents experiencing pain that adversely affected quality of life.

The most robust study of post-vasectomy pain, according to the American Urology Association's Vasectomy Guidelines 2012 (amended 2015) found a rate of 14.7% reported new-onset scrotal pain at 7 months after vasectomy with 0.9% describing the pain as "quite severe and noticeably affecting their quality of life".

For sexually active women who are not pregnant, screening is recommended in those under 25 and others at risk of infection. Risk factors include a history of chlamydial or other sexually transmitted infection, new or multiple sexual partners, and inconsistent condom use. For pregnant women, guidelines vary: screening women with age or other risk factors is recommended by the U.S. Preventive Services Task Force (USPSTF) (which recommends screening women under 25) and the American Academy of Family Physicians (which recommends screening women aged 25 or younger). The American College of Obstetricians and Gynecologists recommends screening all at risk, while the Centers for Disease Control and Prevention recommend universal screening of pregnant women. The USPSTF acknowledges that in some communities there may be other risk factors for infection, such as ethnicity. Evidence-based recommendations for screening initiation, intervals and termination are currently not possible. For men, the USPSTF concludes evidence is currently insufficient to determine if regular screening of men for chlamydia is beneficial. They recommend regular screening of men who are at increased risk for HIV or syphilis infection.

In the United Kingdom the National Health Service (NHS) aims to:

1. Prevent and control chlamydia infection through early detection and treatment of asymptomatic infection;

2. Reduce onward transmission to sexual partners;

3. Prevent the consequences of untreated infection;

4. Test at least 25 percent of the sexually active under 25 population annually.

5. Retest after treatment.

A doppler ultrasound scan of the scrotum is nearly 90% accurate in diagnosis identifying the absence of blood flow in the twisted testicle, which distinguishes torsion from epididymitis.

Radionuclide scanning of the scrotum is the most accurate, imaging technique, but it is not routinely available, particularly with the urgency that might be required. The agent of choice for this purpose is technetium-99m pertechnetate. Initially it provides a radionuclide angiogram, followed by a static image after the radionuclide has perfused the tissue. In the healthy patient, initial images show symmetric flow to the testes, and delayed images show uniformly symmetric activity.

The diagnosis should be made on the history and presenting signs and symptoms. With a convincing history and physical exam immediate surgery is recommended and doppler ultrasound should only be obtained in low suspicion cases to rule out torsion.

Small cysts are best left alone, as are larger cysts that are an asymptomatic condition. Only when the cysts are causing discomfort and are enlarging in size, or the patient wants the spermatocele removed, should a spermatocelectomy be considered. Pain may persist even after removal.

Spermatocelectomy can be performed on an outpatient basis, with the use of local or general anesthesia.

A spermatocelectomy will not improve fertility.

The diagnosis of genital chlamydial infections evolved rapidly from the 1990s through 2006. Nucleic acid amplification tests (NAAT), such as polymerase chain reaction (PCR), transcription mediated amplification (TMA), and the DNA strand displacement amplification (SDA) now are the mainstays. NAAT for chlamydia may be performed on swab specimens sampled from the cervix (women) or urethra (men), on self-collected vaginal swabs, or on voided urine. NAAT has been estimated to have a sensitivity of approximately 90% and a specificity of approximately 99%, regardless of sampling from a cervical swab or by urine specimen. In women seeking an STI clinic and a urine test is negative, a subsequent cervical swab has been estimated to be positive in approximately 2% of the time.

At present, the NAATs have regulatory approval only for testing urogenital specimens, although rapidly evolving research indicates that they may give reliable results on rectal specimens.

Because of improved test accuracy, ease of specimen management, convenience in specimen management, and ease of screening sexually active men and women, the NAATs have largely replaced culture, the historic gold standard for chlamydia diagnosis, and the non-amplified probe tests. The latter test is relatively insensitive, successfully detecting only 60–80% of infections in asymptomatic women, and often giving falsely positive results. Culture remains useful in selected circumstances and is currently the only assay approved for testing non-genital specimens. Other method also exist including: ligase chain reaction (LCR), direct fluorescent antibody resting, enzyme immunoassay, and cell culture.

Because polyorchidism is very uncommon, there is no standard treatment for the condition. Prior to advances in ultrasound technology, it was common practice to remove the supernumerary testicle. Several cases have been described where routine follow-up examinations conducted over a period of years showed that the supernumerary testicle was stable.

A meta-analysis in 2009 suggested removing non-scrotal supernumerary testicles because of the increased risk of cancer, and regular follow-up in the remaining cases to ensure that the supernumerary testicle remains stable.

Some strategies suggested or proposed for avoiding male infertility include the following:

- Avoiding smoking as it damages sperm DNA

- Avoiding heavy marijuana and alcohol use.

- Avoiding excessive heat to the testes.

- Maintaining optimal frequency of coital activity: sperm counts can be depressed by daily coital activity and sperm motility may be depressed by coital activity that takes place too infrequently (abstinence 10–14 days or more).

- Wearing a protective cup and jockstrap to protect the testicles, in any sport such as baseball, football, cricket, lacrosse, hockey, softball, paintball, rodeo, motorcross, wrestling, soccer, karate or other martial arts or any sport where a ball, foot, arm, knee or bat can come into contact with the groin.

- Diet: Healthy diets (i.e. the Mediterranean diet) rich in such nutrients as omega-3 fatty acids, some antioxidants and vitamins, and low in saturated fatty acids (SFAs) and trans-fatty acids (TFAs) are inversely associated with low semen quality parameters. In terms of food groups, fish, shellfish and seafood, poultry, cereals, vegetables and fruits, and low-fat dairy products have been positively related to sperm quality. However, diets rich in processed meat, soy foods, potatoes, full-fat dairy products, coffee, alcohol and sugar-sweetened beverages and sweets have been inversely associated with the quality of semen in some studies. The few studies relating male nutrient or food intake and fecundability also suggest that diets rich in red meat, processed meat, tea and caffeine are associated with a lower rate of fecundability. This association is only controversial in the case of alcohol. The potential biological mechanisms linking diet with sperm function and fertility are largely unknown and require further study.

Bacteria and yeast, including those naturally occurring as part of the human microbiome, can travel along urinary catheters and cause an infection in the bladder, kidneys, and other organs connected to the urinary tract.

CAUTI can lead to complications such as prostatitis, epididymitis, and orchitis in men, and cystitis, pyelonephritis, gram-negative bacteremia, endocarditis, vertebral osteomyelitis, septic arthritis, endophthalmitis, and meningitis in all patients. Complications associated with CAUTI cause discomfort to the patient, prolonged hospital stay, and increased cost and mortality. It has been estimated that more than 13,000 deaths are associated with UTIs annually. Estimated > 560,000 nosocomial UTIs annually.

Ultrasonography of the scrotum is useful when there is a suspicion of some particular diseases. It may detect signs of testicular dysgenesis, which is often related to an impaired spermatogenesis and to a higher risk of testicular cancer. Scrotum ultrasonography may also detect testicular lesions suggestive of malignancy. A decreased testicular vascularization is characteristic of testicular torsion, whereas hyperemia is often observed in epididymo-orchitis or in some malignant conditions such as lymphoma and leukemia. Doppler ultrasonography useful in assessing venous reflux in case of a varicocele, when palpation is unreliable or in detecting recurrence or persistence after surgery, although the impact of its detection and surgical correction on sperm parameters and overall fertility is debated.

Dilation of the head or tail of the epididymis is suggestive of obstruction or inflammation of the male reproductive tract. Such abnormalities are associated with abnormalities in sperm parameters, as are abnormalities in the texture of the epididymis. Scrotal and transrectal ultrasonography (TRUS) are useful in detecting uni- or bilateral congenital absence of the vas deferens (CBAVD), which may be associated with abnormalities or agenesis of the epididymis, seminal vesicles or kidneys, and indicate the need for testicular sperm extraction. TRUS plays a key role in assessing azoospermia caused by obstruction, and detecting distal CBAVD or anomalies related to obstruction of the ejaculatory duct, such as abnormalities within the duct itself, a median cyst of the prostate (indicating a need for cyst aspiration), or an impairment of the seminal vesicles to become enlarged or emptied.

Most cases of polyorchidism are asymptomatic, and are discovered incidentally, in the course of treating another condition. In the majority of cases, the supernumerary testicle is found in the scrotum.

However, polyorchidism can occur in conjunction with cryptorchidism, where the supernumerary testicle is undescended or found elsewhere in the body. These cases are associated with a significant increase in the incidence of testicular cancer: 0.004% for the general population vs 5.7% for a supernumerary testicle not found in the scrotum.

Polyorchidism can also occur in conjunction with infertility, inguinal hernia, testicular torsion, epididymitis, hydrocele testis and varicocele. However, it is not clear whether polyorchidism causes or aggravates these conditions, or whether the existence of these conditions leads sufferers to seek medical attention and thus become diagnosed with a previously undetected supernumerary testicle.

Odynorgasmia, or painful ejaculation, is a physical syndrome described by pain or burning sensation of the urethra or perineum during or following ejaculation. Causes include infections associated with urethritis, prostatitis, epididymitis, as well as use of anti-depressants.