Objective Assessment and treatment of psychological distress in cancer patients was recognized as a major challenge. The role of spouses, caregivers, and significant others became of salient importance not only because of their supportive functions but also in respect to their own burden. The purpose of this study was to assess the amount of distress in a mixed sample of cancer patients and their partners and to explore the dyadic interdependence. Methods An initial sample of 154 dyads was recruited, and distress questionnaires (Hospital Anxiety and Depression Scale, Symptom Checklist 9‐Item Short Version and 12‐Item Short Form Health Survey) were assessed over four time points. Linear mixed models and actor–partner interdependence models were applied. Results A significant proportion of patients and their partners (up to 40%) reported high levels of anxiety, depression, psychological distress, and low quality of life over the course of the investigation. Mixed model analyses revealed that higher risks for clinical relevant anxiety and depression in couples exist for female patients and especially for female partners. Although psychological strain decreased over time, the risk for elevated distress in female partners remained. Modeling patient–partner interdependence over time stratified by patients' gender revealed specific effects: a moderate correlation between distress in patients and partners, and a transmission of distress from male patients to their female partners. Conclusions Our findings provide empirical support for gender‐specific transmission of distress in dyads coping with cancer. This should be considered as an important starting point for planning systemic psycho‐oncological interventions and conceptualizing further research. Copyright © 2013 John Wiley & Sons, Ltd.