The 5% 5‐fluorouracil (5‐FU) cream, considered the gold standard topical treatment, and peeling using 70% glycolic acid (GA) followed by 5% 5‐FU are methods for the treatment of actinic keratoses (AKs). However, the comparison of these two treatments had not yet been described and therefore was the objective of this study. A randomized clinical trial, intrapatient study in which 17 patients received a type of treatment in the right and left upper limb with 5% 5‐FU cream (twice daily) or a peeling application of 70% GA (every 15 days) followed by 5% 5‐FU cream. There was a significant reduction of 75% and 85.71% in the mean number of AK lesions and of 74.5% and 85.71% in the size of lesions on the upper limbs of patients treated with peeling and 5% 5‐FU cream (P‐value ≤.001), respectively. Neither treatment was superior to the other since there was no significant difference (P‐value ≥.05) between the treatments, both at the post‐intervention period as well as when comparing the difference between the pre and post‐intervention periods. The peeling with 70% GA followed by 5% 5‐FU as well as 5% 5‐FU cream are effective methods for the treatment of AKs on upper limbs.