Although often termed a "neurological condition," synesthesia is not listed in either the DSM-IV or the ICD since it most often does not interfere with normal daily functioning. Indeed, most synesthetes report that their experiences are neutral or even pleasant. Like perfect pitch, synesthesia is simply a difference in perceptual experience.

The simplest approach is test-retest reliability over long periods of time, using stimuli of color names, color chips, or a computer-screen color picker providing 16.7 million choices. Synesthetes consistently score around 90% on reliability of associations, even with years between tests. In contrast, non-synesthetes score just 30–40%, even with only a few weeks between tests and a warning that they would be retested.

Grapheme-color synesthetes, as a group, share significant preferences for the color of each letter (e.g. A tends to be red; O tends to be white or black; S tends to be yellow etc.) Nonetheless, there is a great variety in types of synesthesia, and within each type, individuals report differing triggers for their sensations and differing intensities of experiences. This variety means that defining synesthesia in an individual is difficult, and the majority of synesthetes are completely unaware that their experiences have a name.

Neurologist Richard Cytowic identifies the following diagnostic criteria for synesthesia in his "first" edition book. However, the criteria are different in the second book:

1. Synesthesia is involuntary and automatic.

2. Synesthetic perceptions are spatially extended, meaning they often have a sense of "location." For example, synesthetes speak of "looking at" or "going to" a particular place to attend to the experience.

3. Synesthetic percepts are consistent and generic (i.e. simple rather than pictorial).

4. Synesthesia is highly memorable.

5. Synesthesia is laden with affect.

Cytowic's early cases mainly included individuals whose synesthesia was frankly projected outside the body (e.g. on a "screen" in front of one's face). Later research showed that such stark externalization occurs in a minority of synesthetes. Refining this concept, Cytowic and Eagleman differentiated between "localizers" and "non-localizers" to distinguish those synesthetes whose perceptions have a definite sense of spatial quality from those whose perceptions do not.

Synesthesia is found in at least 4.4% of the population, as a high estimate, which is equivalent to 1 in 23 people. This study had also concluded that one common form of synesthesia—grapheme-color synesthesia (colored letters and numbers) – is found in more than one percent of the population, and this latter prevalence of graphemes-color synesthesia has now been independently verified in a yet larger sample. Earlier estimates of the prevalence of synesthesia were based on "best-guess" estimations only ("e.g." 1 in 250,000) or had limitations in their methodologies because they required synesthetes to refer themselves for study ("e.g." 1 in 2000) and for this reason the authors of those studies had been moderate in their claims. Also, some individuals will not self-classify as synesthetes because they do not realize that their perceptions are different from those of everyone else.

The most common forms of synesthesia are those that trigger colors, and the most prevalent of all is day-color. Also relatively common is grapheme-color synesthesia. We can think of "prevalence" both in terms of how common is synesthesia (or different forms of synesthesia) within the population, or how common are different forms of synesthesia within synesthetes. So within synesthetes, forms of synesthesia that trigger color also appear to be the most common forms of synesthesia with a prevalence rate of 86% within synesthetes. In another study, music-color is also prevalent at 18–41%. Some of the rarest are reported to be auditory-tactile, mirror-touch, and lexical-gustatory.

There is research to suggest that the likelihood of having synesthesia is greater in people with autism.

Grapheme-color synaesthesia or colored grapheme synesthesia is a form of synesthesia in which an individual's perception of numerals and letters is associated with the experience of colors. Like all forms of synesthesia, Grapheme-color synesthesia is involuntary, consistent, and memorable. Grapheme-color synesthesia is one of the most common forms of synesthesia, and because of the extensive knowledge of the visual system, one of the most studied.

While it is extremely unlikely that any two synesthetes will report the same colors for all letters and numbers, studies of large numbers of synesthetes find that there are some commonalities across letters (e.g., "A" is likely to be red). Early studies argued that grapheme-color synesthesia was not due to associative learning, such as from playing with colored refrigerator magnets. However, one recent study has documented a case of synesthesia in which synesthetic associations could be traced back to colored refrigerator magnets. Despite the existence of this individual case, the majority of synesthetic associations do not seem to be driven by learning of this sort. Rather, it seems that more frequent letters are paired with more frequent colors, and some meaning-based rules, such as ‘b’ being blue, drive most synesthetic associations.

There has been a lot more research as to why and how synesthesia occurs with more recent technology and as synesthesia has become more well known. It has been found that grapheme-color synesthetes have more grey matter in their brain. There is evidence of an increased grey matter volume in the left caudal intra- parietal sulcus (IPS). There was also found to be an increased grey matter volume in the right fusiform gyrus. These results are consistent with another study on the brain functioning of grapheme-color synesthetes. Grapheme-color synesthetes tend to have an increased thickness, volume, and surface area of the fusiform gyrus. Furthermore, the area of the brain where word, letter, and color processing are located, V4a, is where the most significant difference in make-up was found. Though not certain, these differences are thought to be part of the reasoning for the presence of grapheme-color synesthesia.

Individuals with grapheme-color synesthesia rarely claim that their sensations are problematic or unwanted. In some cases, individuals report useful effects, such as aid in memory or spelling of difficult words.

These experiences have led to the development of technologies intended to improve the retention and memory of graphemes by individuals without synesthesia. Computers, for instance, could use "artificial synesthesia" to color words and numbers to improve usability. A somewhat related example of "computer-aided synesthesia" is using letter coloring in a web browser to prevent IDN homograph attacks. (Someone with synesthesia can sometimes distinguish between barely different looking characters in a similar way.)

Parker and colleagues used a variety of standardised neuropsychological tests in their diagnosis of AJ's hyperthymesia. These included tests of memory, lateralisation, executive functions, language, calculations, IQ, and visual-spatial and visual-motor functions. They also devised novel tests to examine the extent of her memory abilities. These mostly consisted of questions pertaining to specific dates and events in history. Some of her personal recollections were verified with diary entries, as well as by her mother.

More recently, neuroscientist David Eagleman at Baylor College of Medicine developed a free on-line test for hyperthymesia. Participants first give their year of birth, and then are challenged to match dates to 60 famous events that happened between the time they were five years old and the present day. To qualify as potentially hyperthymestic, participants must achieve a score at least three standard deviations above the average. To prevent people from searching for answers on-line during the test, reaction time for each question is measured; answers must be chosen within 11 seconds to qualify for consideration. However, many of the questions are sourced in American culture and test results could have a strong cultural bias against non-Americans.

Hyperthymesia is the condition of possessing an extremely detailed autobiographical memory. People with hyperthymesia remember an abnormally vast number of their life experiences.

American neurobiologists Elizabeth Parker, Larry Cahill, and James McGaugh (2006) identified two defining characteristics of hyperthymesia: spending an excessive amount of time thinking about one's past, and displaying an extraordinary ability to recall specific events from one's past. The word "hyperthymesia" derives from Ancient Greek: "hyper-" ("excessive") and "thymesis" ("remembering").