Objective: The Cancer Threat Interpretation model proposes that clinically significant fear of cancer recurrence/progression (FCR/P) can occur when people misinterpret ambiguous physical symptoms as a sign of recurrence. The aim of this research is to test whether interpretation biases moderate the relationship between pain and FCR/P in women with breast cancer, as predicted. Method: One hundred forty-seven women with breast cancer completed questionnaire measures of demographic and medical information, FCR/P, interpretation bias, and symptom burden, as well as other known predictors of FCR/P. Results: Women with clinically significant levels of FCR/P were more likely to interpret ambiguous words as health-related and experienced more pain than women with levels of FCR/P in the nonclinical range. FCR was associated with both pain (r = .40, p < .001) and interpretation bias (r = .45, p < .001). Interpretation bias and pain (r = .31, p < .001) were also associated with each other. Moderation analyses confirmed that interpretation bias moderated the relationship between pain and FCR (F(1, 143) = 5.76; p = .01). However, this was not the case with FOP (F(1, 143) = .21; p = .65). Conclusion: We found that women with breast cancer with clinically significant FCR/P interpreted ambiguous words as health-related more often and experienced more pain than those with nonclinical FCR/P. Moreover, we found that among those with higher levels of pain, FCR was also higher only among those with higher levels of interpretation bias, as the threat interpretation model predicts.