Pain is the most common side-effect of photodynamic therapy (PDT). Our main objective was to identify pain predictors in PDT. In total, we performed 658 treatments on 377 patients at our department during 2004. Larger sized treatment areas were the strongest pain predictor, and actinic keratoses were more painful to treat than basal cell carcinomas and Bowen's disease. The most sensitive areas to treat were the face and scalp. Gender and age did not influence pain. Although treatment outcome was not our primary objective, 62% of 95 superficial basal cell carcinomas that were followed for 3 years showed complete clearance. Also, perforation of nodular basal cell carcinomas did not lead to better clinical results. In conclusion, the size of the treatment area, the diagnosis and the lesion location influence pain during PDT. Nevertheless, there is a large variance in visual analogue scale assessment within each group, thereby limiting the ability to predict pain.