Abstract The Brief Symptom Inventory-18 (BSI-18) is a self-reporting screening instrument that is widely used to assess global psychological distress and three kinds of symptoms: anxiety, depression, and somatization. The present study tests the factor structure of the BSI-18 using confirmatory factor analysis (CFA), its reliability, convergent validity, and invariance for both sexes. A heterogeneous sample of 1183 cancer patients completed the BSI 18 and the NCCN Problem List. Hierarchical models of three and four subscales with GSI as a main factor provided an adequate and similar model fit. Nonetheless, the hierarchical three-factor model (the theoretical proposal) was selected for methodological and theoretical reasons. Reliability indexes (Cronbach's alpha and Composite Reliability) were satisfactory. The positive significant associations between BSI-18 (GSI and subscales) and emotional and physical categories of the Problem List showed the suitable convergent validity of the instrument. Finally, multigroup CFA revealed an essentially invariant structure of the BSI-18 for both sexes. The BSI-18 is a short instrument that can be used by researchers and health professionals to assess the psychological distress of cancer survivors.