The purpose of this study was to investigate potential predictors (patient variables) that would result in oncology nurses' recognition of and response to patient-initiated humor (PIH). Participants included 47 nurses of an 80-member Oncology Nursing Society chapter (57% response rate), which yielded 232 usable vignettes. Previously collected qualitative data of patient-nurse conversations were used to construct simulated vignettes using a factorial survey design. Five randomly generated vignettes containing 14 independent patient variables with different levels were used to examine nurses' identification of PIH. The unit of analysis in factorial survey is the vignette. Multiple regression and analysis of variance were used to analyze variables in each vignette. Two of 14 variables were significant: "verbal" (actual words the patient spoke) and "intonation" (inflection, pitch, or manner of speech). A 2×2 factorial analysis of variance using verbal and intonation variables revealed that oncology nurses' recognition of and response to PIH were primarily predicted by patients' verbal words. This study distinguishes PIH as a patient-initiated behavior rather than nurse-driven interventions and is a new venue for research in patient-nurse interactions. Results demonstrate the central role of patient-centered communication to inform clinical practice about patient preferences, individualized integration/participation in their care, and a knowledge base of patient-centered behaviors for outcomes of personal importance.