Population‐based studies have reported an increased incidence of skin cancer in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We have examined the risk factors for non‐melanoma skin cancer (NMSC) in patients diagnosed with ET or PV during 1973–2012.

A case–control study was performed to compare the clinical and treatment‐related data of 51 ET/PV patients who had NMSC with that of 401 patients who did not. We also evaluated whether polymorphisms in 12 genes involved in DNA integrity predisposed to NMSC.

By multivariate logistic regression analysis, risk factors for NMSC were older age (OR: 1.7, 95% CI: 1.3–2.1, P < 0.001), male sex (OR: 2.1, 95% CI: 1.1–3.8, P = 0.023), higher cumulated hydroxycarbamide dose (OR: 1.3, 95% CI: 1.1–1.7, P = 0.017), and busulphan exposure (OR: 3.2, 95% CI: 1.05–10.0, P = 0.041). On the time‐to‐event prognostic model, factors independently associated with increased cumulative incidence of NMSC were age (5% increased risk per year; P < 0.001), male sex (91% increased risk; P = 0.022), and hydroxycarbamide exposure (22% increased risk; P = 0.065). No susceptibility gene variant was identified.

These findings suggest that the risk to develop NMSC in ET/PV patients results from the combined effect of common risk factors (age, male sex) together with cytoreductive treatment.