Objective To develop an analysis scheme capturing the cognitive processes underlying QoL assessment to increase our understanding on how to interpret responses to QoL items. Tourangeau et al.'s (The psychology of survey response, 2000) and Rapkin and Schwartz' (Health Qual Life Outcomes 2:14, 2004) cognitive process models form the basis for this analysis scheme. Methods We conducted think aloud interviews with six cancer patients prior to and following radiotherapy to elicit the cognitive processes underlying the assessment of 7 EORTC QLQ-C30 items. Content analysis was carried out by two to four researchers independently. Eighty text fragments were analyzed inductively and combined in an iterative process with deductive analyses based on both models.Results We have developed a comprehensive analysis scheme feasible for analyzing the cognitive processes underlying QoL assessment qualitatively. All cognitive components of both models could be distinguished in our data. The cognitive component 'reporting and response selection' needed extension to fully capture the cognitive processes used. Conclusion The two models combined are useful in describing the cognitive processes cancer patients use in answering QoL items, and as such facilitate insight into patients' self-reported QoL assessments. Interestingly, the content of the cognitive processes not only differed between patients but also between items within patients and over time.