This study examined the impact of personal and family cancer history on psychological distress. Regression analyses were conducted on a nationally representative sample of adult individuals who participated in the 2000 National Health Interview Survey, USA. Effects on distress of a personal cancer history, any family cancer history, or mother, father, sister or brother with a cancer history were examined. The interaction of personal and family cancer histories and three-way interactions with gender were also assessed. Analyses indicate that having either a personal or family cancer history is linked with significantly greater psychological distress and there is evidence of an interaction. Three-way interactions with gender were not found. Consistent with prior research, results demonstrated that cancer survivors are more distressed than the general population. Results extend prior research by indicating that having a first-degree relative with cancer increases risk for distress, and having personal and family cancer histories may exert a synergistic effect on distress.