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Previous research indicates that men are affected when their female partners have breast cancer. However, little is known about what predicts men’s psychological well-being in this context. The current investigation involved couples in which the woman had early stage breast cancer and explored the degree to which men’s positive and negative well-being was related to women’s well-being, women’s physical symptoms, relationship functioning, and relationship duration. The findings indicate that all of these factors play a role and interact in predicting men’s well-being. In particular, when women have a high level of physical symptoms, the typical associations between men’s well-being with women’s well-being and relationship adjustment no longer persist. Implications for working with couples addressing health problems are provided.