There is increasing epidemiological evidence for a role of allergic/atopic disorders in cancer development. However, findings have been inconsistent, which may be partly due to differences in defining allergy and the associated atopic disorders. The use of a biological marker for atopy may enhance the exploration of the association with cancer risks. To examine the association of atopy with common malignancies, we compared the prevalence of atopy in 318 patients with prostate cancer, 381 patients with breast cancer, 196 patients with lung cancer, 477 patients with colorectal cancer and 4,271 controls in a case-control analysis of participants of 2 prospective studies conducted in Saarland, Germany. Data on physician-diagnosed atopy-related diseases (asthma, hay fever and atopic dermatitis) were obtained by self-administered questionnaire. Allergen-specific immunoglobulin E (IgE) was assessed among cases and controls to define atopy. We observed a significantly increased risk of prostate cancer (odds ratio (OR) 1.35, 95% confidence interval (CI) 1.00–1.83) and a tentatively, statistically not significant increased risk of breast cancer (OR 1.20, 95% CI 0.87–1.66) and lung cancer (OR 1.29, 95% CI 0.87–1.92) with specific IgE positivity. No consistent associations were found with atopy-related diseases. Our findings are consistent with other epidemiological evidence suggesting an increased risk of prostate cancer with atopy and indicate a complex association between atopy/atopy-related diseases and cancer risk that varies by type of atopy-related disorders and the particular type of cancer under consideration. The effect on cancer risk by atopy, defined by IgE reactivity, may differ from the effect by atopy-related clinically defined diseases such as asthma, hay fever and atopic dermatitis.