OBJECTIVE: To develop an instrument to measure HRQoL in patients with advanced colorectal cancer (ACC) given that there are no specifically designed for this purpose. METHODS: In order to define the main dimensions the questionnaire should cover, a scientific literature review, a specific interview and a focus group with seven experts (four oncologists, two nurses and one psychologist) were performed. Later, an in depth semistructured interview was conducted in eight patients with ACC to evaluate the impact of disease symptoms and treatment in HRQoL. From the content of the interviews a sample of items were identified. Each item was subsequently rated by the same panel of experts, according to clarity, frequency and importance to patients with ACC (qualitative reduction). Remaining items were edited in the questionnaire form in order to be self-administrated to a sample of 35 patients in a cross-sectional study. After that, a factor analysis and a Rasch analysis were performed to obtain the final questionnaire. RESULTS: Twelve dimensions were identified by experts. From the qualitative analysis, a questionnaire with 27 item was obtained, 4 items were only applicable to a specific subset of patients (items analysed independently). Factor analysis from the remaining 23 items identified 4 dimensions explaining 56.14 % of total variance. In each dimension the Rasch analysis was used to exclude those items with inadequate adjustment (INFIT>1.30) or redundant with other items in the measurement scale, obtaining in total 16 items. The final questionnaire includes 16 items with a good internal consistency (Cronbach's alpha = 0.81) and 4 additional items that have to be analysed separately. CONCLUSION: A new questionnaire was elaborated to measure HRQoL in patients with ACC with a good reliability. Psychometric properties are currently being tested in conditions of real clinical practice.