BACKGROUND: Disseminated superficial actinic porokeratosis (DSAP) is a chronic cutaneous disorder of keratinization for which there is no known cure. Current therapies are often ineffective, painful, or unappealing. OBJECTIVE: To investigate the efficacy and safety of diclofenac sodium 3% gel for the treatment of DSAP. METHODS: Seventeen adult patients with a diagnosis of DSAP applied diclofenac sodium 3% gel to a target area (forearm) twice daily for 3 months up to a maximum of 6 months in an open-label, multicentre pilot study. Target area lesion counts were performed monthly, and global lesion counts were performed at baseline and at weeks 12 and 24. A treatment satisfaction questionnaire was completed at weeks 12 and 24. RESULTS: Thirteen patients completed 12 weeks of treatment and 10 completed 24 weeks. Among patients who completed 12 weeks, there was a mean decrease of 4% in target area lesions, while a mean increase of 12% was noted in global lesions. Among patients who completed 24 weeks, there was a mean increase of 19% in global lesions, but only a 10% increase noted in the target area. Seven of 13 patients had a decrease in target area lesions at week 12 and 3 of 10 patients at week 24. Questionnaire responses indicated 6 out of 10 patients would use the medication again. CONCLUSION: Target area DSAP lesions in the majority of patients treated with diclofenac sodium 3% gel (both 12 and 24 weeks) progressed to a lesser extent as compared to the global lesion count.