In patients with clinical signs that may indicate a colorectal cancer, physicians may interpret the presence of a comorbid depressive mood as either increasing or decreasing the likelihood of cancer diagnosis. This study examined the association between depressive mood in candidates for a colonoscopy and subsequent diagnosis of cancer. Ninety-four outpatients [35 men, mean age ± standard deviation (SD) = 56.2 ± 9.8 years, 59 women, mean age ± SD = 54.2 ± 12.9 years] were given the 13-item Beck Depression Inventory to assess depressive mood before undergoing a colonoscopy. Additional psychological, demographic, and clinical data were collected prior to the colonoscopy. The colonoscopy found a cancer in 18 patients (19.1%). Cancer patients were older (P = 0.015) and more likely to present with anemia (P < 0.001) and unexplained weight loss (P = 0.046). Depressive mood was associated with a subsequent diagnosis of cancer in women (P = 0.007), but not in men (P = 0.985). This association remained significant after adjustment for potential confounders in women (i.e. anemia and unexplained weight loss) (P = 0.014). In women with clinical signs that warrant a colonoscopy, comorbid depressive mood may be associated with an increased likelihood of colorectal cancer and should not delay the receipt of a guideline-based diagnosis procedure.