Objective We examined differences in distress levels and Distress Thermometer (DT) cutoff scores between different cancer types. The effect of socio‐demographic and illness‐related variables on distress was also examined. Methods One thousand three hundred fifty patients (response = 51%) completed questions on socio‐demographic and illness‐related variables, the Dutch version of the DT and Problem List, and the Hospital Anxiety and Depression Scale. Receiver operating characteristics analyses were performed to determine cancer specific cutoff scores. Univariate and multivariate effects of socio‐demographic and illness‐related variables (including cancer type) on distress were examined. Results Prostate cancer patients reported significantly lower DT scores (M = 2.5 ± 2.5) and the cutoff score was lower (≥4) than in patients with most other cancer types (M varied between 3.4 and 5.1; cutoff ≥ 5). Multivariate analyses (F = 10.86, p < .001, R2 = 0.08) showed an independent significant effect of four variables on distress: intensive treatment (β = .10, any (combination of) treatment but surgery only and ‘wait and see’); a non‐prostate cancer type (β = −.17); the interaction between gender and age (β = −.12, highest distress in younger women as compared with older women and younger and older men); and the interaction between cancer type and treatment intensity (β = .08, lowest scores in prostate cancer patients receiving non‐intensive treatment as compared with their counterparts). Conclusions Distress and cutoff score in prostate cancer patients were lower than in patients with other cancer types. Additionally, younger women and patients receiving treatment other than surgery only or ‘wait and see’ are at risk for higher distress. These results can help identify patients possibly in need of referral to professional psychosocial and/or allied health care. Copyright © 2012 John Wiley & Sons, Ltd.