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One goal of the Patient-Reported Outcomes Measurement Information System™ (PROMIS™) is to develop a measure of sexual functioning that broadens the definition of sexual activity and incorporates items that reflect constructs identified as important by patients with cancer. We describe how cognitive interviews improved the quality of the items and discuss remaining challenges to assessing sexual functioning in research with cancer populations. We conducted 39 cognitive interviews of patients with cancer and survivors on the topic of sexual experience. Each of the 83 candidate items was seen by 5–24 participants. Participants included both men and women and varied by cancer type, treatment trajectory, race, and literacy level. Significantly revised items were retested in subsequent interviews. Cognitive interviews provided useful feedback about the relevance, sensitivity, appropriateness, and clarity of the items. Participants identified broad terms (e.g., “sex life”) to assess sexual experience and exposed the challenges of measuring sexual functioning consistently, considering both adjusted and unadjusted sexual experiences. Cognitive interviews were critical for item refinement in the development of the PROMIS measure of sexual function. Efforts are underway to validate the measure in larger cancer populations. [ABSTRACT FROM AUTHOR]