Photodynamic therapy (PDT) with topical application of either aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) is increasingly used for the treatment of actinic keratoses (AKs). Although PDT is a well-tolerated treatment, pain is the most severe side effect. Sixty-nine patients (mean age 69 years, 61 male, 8 female) suffering from multiple AKs on the scalp (field cancerization) were included in the study. PDT treatment was performed, using red light (Waldmann PDT 1200) with a light dose of 100 J/cm2 delivered at a dose rate of 160 mW/cm2. Either ALA or MAL were used as photosensitizer. Patients were asked to rate their pain on a scale from 0 to 10 (0 = no pain, 10 = unbearable pain). Upon reaching a score of 10 treatment was discontinued. Comparison of ALA and MAL in patients with AK revealed that MAL induced less pain than ALA. While 14% of the patients treated with MAL discontinued treatment before reaching the required light dose of 100 J/cm2, the number of patients treated with ALA who discontinued treatment reached 54%. PDT using MAL appears to be a better tolerated treatment for multiple AKs on the scalp compared to ALA-PDT. Differences in selectivity for tumor cells and transport of ALA in peripheral neurons may play a role.