In the present study, we demonstrated that the p16INK4a protein, encoded by the CDKN2A gene, is significantly accumulated in three types of hyperpigmented spots—solar lentigo, melasma, and acne-induced PIH—as evidenced by immunofluorescent staining, with its prevalence predominantly in the epidermis as shown in Figure 1. This evidence concerns the gene CDKN2A and freckles.