Background: Hand eczema and hand psoriasis are common skin conditions that may present with similar clinical features, making differentiation challenging.Objective: This study aims to identify clinical characteristics that distinguish hand eczema from hand psoriasis.Methods: A retrospective chart review was conducted on patients diagnosed with either condition at the Contact Dermatitis and the Psoriasis Clinic of the Department of Dermatology, Siriraj Hospital, Mahidol University-a national tertiary referral center in Thailand-from January 2015 to November 2022.Results: A total of 398 patients with hand eczema and 140 with hand psoriasis were included. Exogenous (76.1%) and endogenous (23.9%) hand eczema showed similar lesion location and morphology. However, compared with hand psoriasis, endogenous hand eczema more commonly involved the palmar area, palmar side of digits, and finger pulps (P < 0.001). Conversely, hand psoriasis predominantly affected both sides of the wrist, the dorsal side of the hand, nail fold, and the nails (P < 0.001). Clinical manifestations such as papules, vesicles, scales, and fissures were more frequently observed in endogenous hand eczema, whereas hyperkeratotic plaques were more characteristic of hand psoriasis (P < 0.001). Itching was significantly more frequent in hand eczema (P < 0.001).Conclusions: Symptoms, lesion locations, and morphology may provide valuable insights that enhance diagnostic accuracy in distinguishing between hand eczema and psoriasis.