Background <p>Leprosy is a chronic infectious disease with diverse clinical manifestations. Skin lesions may present as erythema, nodules, ulcers, bullae, or verrucous hyperplasia. When skin lesions and neurological symptoms are atypical, misdiagnosis is common. When patients develop rare skin lesions resembling pretibial myxedema, clinicians often misdiagnose the condition as hyperthyroidism or mucin deposition disorders. Such misdiagnoses can delay appropriate treatment and may lead to serious complications.</p> Case presentation <p>We report a 74-year-old male with progressive bilateral pretibial edema and multiple translucent nodular lesions for over six months, accompanied by intermittent high-grade fever. The skin lesions were repeatedly misinterpreted as pretibial myxedema despite the absence of Graves’ disease and the presence of only subclinical hypothyroidism. Repeated bacterial smears obtained from ulcer exudates were negative, which may have contributed to further delaying diagnosis. Histopathological examination of nodular lesions revealed diffuse infiltration of foamy histiocytes with a heavy acid-fast bacillary load, confirming multibacillary leprosy with type 2 lepra reaction (erythema nodosum leprosum). Treatment with rifampicin and clofazimine, combined with systemic corticosteroids, resulted in rapid clinical improvement.</p> Conclusion <p>Pretibial myxedema-like lesions in this patient represented chronic edema and nodular changes associated with lepromatous leprosy rather than true pretibial myxedema. This case highlights a common diagnostic pitfall and underscores the importance of early histopathological evaluation and heightened clinical suspicion to prevent delayed diagnosis and irreversible complications.</p> Clinical trial <p>Not applicable.</p>