The Goeckerman regimen (GR) is one of the oldest effective treatments for psoriasis. It involves daily dermal application of crude coal tar with dermal exposure to ultraviolet (UV) radiation. A study was carried out to evaluate the genotoxic risk of GR by comparing p53 protein plasma level and chromosomal aberrations (CA) in peripheral lymphocytes in 33 patients with psoriasis, before and after GR. Psoriasis Area and Severity Index (PASI) was used to evaluate the efficacy of GR. PASI significantly decreased after GR (P < 0.001), confirming the excellent efficacy of the treatment, However, significant increases in level of p53 protein (P < 0.05) and CA (P < 0.001) after treatment indicates that this method carries an increased genotoxic risk in patients with psoriasis.