Although many researchers in psychology, religious studies, and psychiatry recognize that there is overlap in the experiences their subjects recount, disciplinary silos and challenges involved in comparing reported experiences have left us with little understanding of the mechanisms, whether biological, psychological, and/or sociocultural, through which these experiences are represented and differentiated. So-called mystical experiences, which some psychologists view as potentially sui generis, provide a test case for assessing whether we can develop an expanded framework for studying unusual experiences across disciplines and cultures. Evidence for the special nature of “mystical experience” rests on the operationalization of a metaphysically untestable construct in two widely used self-report scales: the Mysticism Scale and the Mystical Experiences Questionnaire. Consideration of the construct in light of research on alterations in sense of self induced by psychoactive drugs and meditation practices suggests that “positive experiences of undifferentiated unity” are not sui generis, but rather a type of “ego dissolution.” To better understand the nature and effects of unusual experiences, such as alterations in the sense of self, we need self-report measures that distinguish between generically worded experiences and the way they are appraised in terms of valence, significance, cause, and long-term effects in different contexts.