Recently, focal chemical peels with trichloroacetic acid (TCA) have been introduced for the treatment of pigmentary disorders to minimize the side effects such as pain or scarring associated with medium-to-deep chemical peeling. This is a controlled, prospective study to compare the efficacy of a focal medium-depth chemical peel regimen using 70% glycolic acid and 35% TCA with cryosurgery, in the treatment of solar lentigines of the hands. Twenty-five patients were treated with either focal medium-depth chemical peel or cryosurgery, which was randomly assigned to the left or right hand. Clinical improvement was graded by the three blinded investigators 2-months after the treatment. In the focal medium-depth chemical peel treated side, clearing was achieved in four out of 23 patients (17.4%) compared with five out of 23 patients (21.7%) in the cryosurgery treated side. Statistically, the difference between the clinical improvement of solar lentigines with chemical peel and cryosurgery was not significant, according to chi-square test (p = 0.940). However, we suggest that treatment of the solar lentigines with a focal medium-depth chemical peel may be clinically superior to treatment with cryosurgery, due to the paucity of side effects, such as hypopigmentation and pain, associated with the chemical peel regimen.