2 patients with widespread porokeratosis Mibelli (PM) were treated orally with RO 10-9359. The dose was 75 mg/day for 10 days, then 50 mg/day for 3 weeks. The drug produced a good improvement of condition with no serious side effect. Ultrastructural examination of a healed lesion showed the presence of a fine granular substance in the intercellular space of the spinous layer, most likely produced by keratinocytes; ultrastructural cellular alterations of PM were still evident and the lesion recurred after suspension of treatment.