Investigations by the physician include imaging (ultrasound, CAT scan, MRI) and, if possible, obtaining a tissue diagnosis by biopsy, hysteroscopy, or D&C.

Ultimately the diagnosis is established by the histologic examination of the specimen. Typically malignant lesions have >10 mitosis per high power field. In contrast a uterine leiomyoma as a benign lesion would have < 5 mitosis per high power field.

Unusual or postmenopausal bleeding may be a sign of a malignancy including uterine sarcoma and needs to be investigated. Other signs include pelvic pain, pressure, and unusual discharge. A nonpregnant uterus that enlarges quickly is suspicious. However, none of the signs are specific. Specific screening test have not been developed; a Pap smear is a screening test for cervical cancer and not designed to detect uterine sarcoma.

The prognosis is determined primarily by the cancer stage. Most tumours are discovered at an early stage and have a good prognosis, especially when compared to uterine carcinosarcoma. Five year survival for stage I and stage III tumours is approximately 80% and 50% respectively.

Endometrial polyps are usually benign although some may be precancerous or cancerous. About 0.5% of endometrial polyps contain adenocarcinoma cells. Polyps can increase the risk of miscarriage in women undergoing IVF treatment. If they develop near the fallopian tubes, they may lead to difficulty in becoming pregnant. Although treatments such as hysteroscopy usually cure the polyp concerned, recurrence of endometrial polyps is frequent. Untreated, small polyps may regress on their own.

Prognosis of the UPSC is affected by age, stage, and histology as well as treatment.

In the older literature survival rates have been given as 35–50% for Stage I–II and 0–15% for Stage III and IV UPSC, More recently it was reported that forty-two percent of 138 patients were found disease-free at five years.

In 2009, the journal of "Gynecologic Oncology" reported the following 5-year survival rates based upon stage of cancer:

- Stage I: 50% - 80%

- Stage II: 50%

- Stage III: 20%

- Stage IV: 5% - 10%

Endometrial polyps can be detected by vaginal ultrasound (sonohysterography), hysteroscopy and dilation and curettage. Detection by ultrasonography can be difficult, particularly when there is endometrial hyperplasia (excessive thickening of the endometrium). Larger polyps may be missed by curettage.

Endometrial polyps can be solitary or occur with others. They are round or oval and measure between a few millimeters and several centimeters in diameter. They are usually the same red/brown color of the surrounding endometrium although large ones can appear to be a darker red. The polyps consist of dense, fibrous tissue (stroma), blood vessels and glandlike spaces lined with endometrial epithelium. If they are pedunculated, they are attached by a thin stalk (pedicle). If they are sessile, they are connected by a flat base to the uterine wall. Pedunculated polyps are more common than sessile ones.

Uterine adenosarcomas are typically treated with a total abdominal hysterectomy and bilateral salpingoophorectomy (TAH-BSO). Ovary sparing surgery may be done in women wishing to preserve fertility.

A pelvic examination may detect an adnexal mass. A CA-125 blood test is a nonspecific test that tends to be elevated in patients with tubal cancer. More specific tests are a gynecologic ultrasound examination, a CT scan, or an MRI of the pelvis.

Occasionally, an early fallopian tube cancer may be detected serendipitously during pelvic surgery.

Prognosis depends to a large degree on the stage of the condition. In 1991 it was reported that about half of the patients with advanced stage disease survived 5 years with a surgical approach followed by cisplatinum-based chemotherapy.

Prognosis of the CC is affected by age, stage, and histology as well as treatment

The primary treatment is surgical. FIGO-cancer staging is done at the time of surgery which consists of peritoneal cytology, total hysterectomy, bilateral salpingo-oophorectomy, pelvic/para-aortic lymphadenectomy, and omentectomy. The tumor is aggressive and spreads quickly into the myometrium and the lymphatic system. Thus even in presumed early stages, lymphadenectomy and omentectomy should be included in the surgical approach. If the tumor has spread surgery is cytoreductive followed by radiation therapy and/or chemotherapy.

The five years survival was reported to be 68%.

The presence of a uterine fibroid versus an adnexal tumor is made. Fibroids can be mistaken for ovarian neoplasms. An uncommon tumor which may be mistaken for a fibroid is Sarcoma botryoides. It is more common in children and adolescents. Like a fibroid, it can also protrude from the vagina and is distinguished from fibroids. While palpation used in a pelvic examination can typically identify the presence of larger fibroids, gynecologic ultrasonography (ultrasound) has evolved as the standard tool to evaluate the uterus for fibroids. Sonography will depict the fibroids as focal masses with a heterogeneous texture, which usually cause shadowing of the ultrasound beam. The location can be determined and dimensions of the lesion measured. Also, magnetic resonance imaging (MRI) can be used to define the depiction of the size and location of the fibroids within the uterus.

Imaging modalities cannot clearly distinguish between the benign uterine leiomyoma and the malignant uterine leiomyosarcoma, however, the latter is quite rare. Fast growth or unexpected growth, such as enlargement of a lesion after menopause, raise the level of suspicion that the lesion might be a sarcoma. Also, with advanced malignant lesions, there may be evidence of local invasion. A biopsy is rarely performed and if performed, is rarely diagnostic. Should there be an uncertain diagnosis after ultrasounds and MRI imaging, surgery is generally indicated.

Other imaging techniques that may be helpful specifically in the evaluation of lesions that affect the uterine cavity are hysterosalpingography or sonohysterography.

Leiomyoma is the most common benign mesenchymal tumor of esophagus and second most common benign tumor of the small bowel (with gastrointestinal stromal tumor as most common). Although leiomyoma is the most common benign esophageal tumor, malignant carcinoma is still 50 times more likely. Approximately 50% of cases are found in the jejunum, followed by the ileum in 31% of cases. Almost one half of all lesions are less than 5 centimeters.

About 1 out of 1000 lesions are or become malignant, typically as a leiomyosarcoma on histology. A sign that a lesion may be malignant is growth after menopause. There is no consensus among pathologists regarding the transformation of leiomyoma into a sarcoma.

The lesion is found in patients who present typically with abnormal or postmenopausal bleeding or discharge. Such bleeding is followed by further evaluation leading to a tissue diagnosis, usually done by a dilatation and curettage (D&C). A work-up to follow would look for metastasis using imaging technology including sonography and MRI. The median age at diagnosis in a large study was 66 years. Histologically the lesion may coexist with classical endometrial cancer.

Uterine cancer resulted in about 58,000 deaths in 2010 up from 45,000 in 1990.

Uterine cancer is the fourth most common cancer in women in the UK (around 8,500 women were diagnosed with the disease in 2011), and it is the tenth most common cause of cancer death in women (around 2,000 people died in 2012).

Adenomyosis can vary widely in the extent and location of its invasion within the uterus. As a result, there are no established pathognomonic features to allow for a definitive diagnosis of adenomyosis through non-invasive imaging. Nevertheless, non-invasive imaging techniques such as transvaginal ultrasonography (TVUS) and magnetic resonance imaging (MRI) can both be used to strongly suggest the diagnosis of adenomyosis, guide treatment options, and monitor response to treatment. Indeed, TVUS and MRI are the only two practical means available to establish a pre-surgical diagnosis.

Differential diagnosis of this condition includes the Birt-Hogg-Dubé syndrome and tuberous sclerosis. As the skin lesions are typically painful, it is also often necessary to exclude other painful tumors of the skin (including blue rubber bleb nevus, leiomyoma, eccrine spiradenoma, neuroma, dermatofibroma, angiolipoma, neurilemmoma, endometrioma, glomus tumor and granular cell tumor; the mnemonic "BLEND-AN-EGG" may be helpful). Other skin lesions that may need to be considered include cylindroma, lipoma, poroma and trichoepithelioma; these tend to be painless and have other useful distinguishing features.

The skin lesions may be difficult to diagnose clinically but a punch biopsy will usually reveal a Grenz zone separating the tumour from the overlying skin. Histological examination shows dense dermal nodules composed of elongated cells with abundant eosinophilic cytoplasm arranged in fascicles (spindle cells). The nuclei are uniform, blunt-ended and cigar-shaped with only occasional mitoses. Special stains that may be of use in the diagnosis include Masson's trichrome, Van Gieson's stain and phosphotungstic acid–haematoxylin.

The renal cell carcinomas have prominent eosinophilic nucleoli surrounded by a clear halo.

Surgery, with as wide a margin of removal as possible, has generally been the most effective and preferred way to attack LMS. If surgical margins are narrow or not clear of tumor, however, or in some situations where tumor cells were left behind, chemotherapy or radiation has been shown to give a clear survival benefit. While LMS tends to be resistant to radiation and chemotherapy, each case is different and results can vary widely.

LMS of uterine origin do frequently, but not always respond to hormonal treatments.

The terms uterine cancer and womb cancer may refer to any of several different types of cancer which occur in the uterus, namely:

- Endometrial cancer:

- Cervical cancer arises from the transformation zone of the cervix, the lower portion of the uterus and connects to the upper aspect of the vagina.

- Uterine sarcomas: sarcomas of the myometrium, or muscular layer of the uterus, are most commonly leiomyosarcomas.

- Gestational trophoblastic disease relates to neoplastic processes originating from tissue of a pregnancy that often is located in the uterus.

The diagnose of adenomyosis is through a pathologist microscopically examining small tissue samples of the uterus. These tissue samples can come from a uterine biopsy or directly following a hysterectomy (surgery to remove the uterus). Uterine biopsies can be obtained by either a laparoscopic procedure through the abdomen or hysteroscopy through the vagina and cervix. The diagnosis is established when the pathologist can find invading clusters of endometrial tissue within the myometrium. Several diagnostic criterion can be used, but typically they require either the endometrial tissue to have invaded greater than 2% of the myometrium, or a minimum depth of invasion such as 1–4 mm.

Mesenchymal neoplasms of the gallbladder are rare and in particular leiomyomas of the gallbladder have been rarely reported, all of them in patients with immune system disorders. Although, recently, a case was reported in absence of associated immunodeficiency at Monash Hospital in Melbourne Australia in a healthy 39-year-old woman with no symptoms.

The differential diagnosis of serous carcinoma not otherwise specified includes:

- Ovarian serous carcinoma, a type of ovarian cancer.

- Uterine serous carcinoma, also known as "uterine papillary serous carcinoma", a type of uterine cancer.

- Fallopian tube serous carcinoma, a type of uterine tube cancer.

- Cervical serous carcinoma, a rare type of cervical cancer.

- Primary peritoneal serous carcinoma, a very rare cancer that arise from the peritoneum.

There has been the suggestion that the above diagnoses really represent one entity.

In addition to being named based on the tissue of origin, sarcomas are also assigned a grade (low, intermediate, or high) based on the presence and frequency of certain cellular and subcellular characteristics associated with malignant biological behavior. Low grade sarcomas are usually treated surgically, although sometimes radiation therapy or chemotherapy are used. Intermediate and high grade sarcomas are more frequently treated with a combination of surgery, chemotherapy and/or radiation therapy. Since higher grade tumors are more likely to undergo metastasis (invasion and spread to locoregional and distant sites), they are treated more aggressively. The recognition that many sarcomas are sensitive to chemotherapy has dramatically improved the survival of patients. For example, in the era before chemotherapy, long-term survival for patients with localized osteosarcoma was only approximately 20%, but now has risen to 60–70%.