This longitudinal study has examined the associations between perceived supportive and unsupportive spousal behavior and changes in distress in couples coping with cancer. We tested whether people relatively low in their sense of personal control were more responsive to spousal supportive and unsupportive behavior than were people relatively high in personal control. Patients with colorectal cancer and their partners (n = 70) completed questionnaires at two assessment points: 3 (at baseline) and 9 months (at follow-up) after the diagnosis. We assessed perceived spousal supportive (SSL) and unsupportive (SSL-N) behavior, sense of personal control (Pearlin & Schooler's Mastery), and depressive symptoms (CES-D) in both patients and partners. Multilevel analysis (MLwiN) was used to examine changes in distress over time in a dyadic context. Patients and partners who perceived more spousal support reported less distress over time, but this only applied to those relatively low in personal control. Moreover, partners who perceived more unsupportive spousal behavior reported more distress, again only if they were relatively low in personal control. Patients and partners relatively high in personal control reported relatively low levels of distress, regardless of spousal behavior. In conclusion, people relatively low in personal control may be more adversely affected by unsupportive behavior and benefit more from supportive behavior than people relatively high in personal control.