Background: Lichen simplex chronicus is a troublesome intractable itchy dermatosis, which may persist despite intensive topical treatments. Recently it has been demonstrated that topical aspirin solution with dichloromethane has a significant antipruritic effect in an experimentally induced itch. Objective: The aim of this double-blind, crossover placebo trial was to evaluate the efficacy of this solution in the treatment of lichen simplex chronicus. Methods: Twenty-nine patients with lichen simplex chronicus of at least 3 months' duration that did not respond to topical corticosteroids were randomized in a double-blind fashion to receive aspirin/dichloromethane solution in treatment period 1 for 2 weeks followed by placebo in treatment period 2 or placebo followed by aspirin in period 2 with a crossover design after a 2-week washout. The patients rated the pruritus intensity before and during therapy with a visual analog scale; a blinded investigator performed photographic assessment. Results: A significant therapeutic response was achieved in 11 (46%) of the patients who completed the study compared with 3 patients (12%) receiving placebo. Overall, aspirin-treated patients experienced an average decrease in the visual analog scale of 2.18 ± 2.86 versus 0.69 ± 2.31 of those receiving placebo. The difference between the 2 treatments for week 2 was significant (P = .03). Conclusion: The study suggests that topical aspirin/dichloromethane might be a practical treatment for lichen simplex chronicus. (J Am Acad Dermatol 2001;45:910-3.)