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Lipomas are among the most common benign soft-tissue tumors; however, their occurrence in the hand is uncommon, and giant lipomas in this location are particularly rare. Due to the limited anatomical space in the hand, these lesions can cause functional impairment and compression symptoms. We present the case of a 73-year-old woman who presented for evaluation with a six-year history of a mass in the right thenar region that had been progressively increasing in size, accompanied by pain during active thumb movements (flexion, adduction, and opposition), paresis, and decreased pinch strength. Physical examination revealed a soft, mobile mass with mild tenderness on palpation and reduced range of motion in the thumb. Imaging studies revealed a well-defined lipomatous lesion measuring 5 × 3 cm, with no findings suggestive of malignancy. The lipoma was excised via a thenar approach, revealing a well-encapsulated mass located beneath the flexor pollicis brevis muscle, with no involvement of adjacent neurovascular or tendinous structures. A complete resection was performed, and histopathological evaluation confirmed the diagnosis of lipoma. The patient had an uneventful postoperative course, and no complications were observed during follow-up. Although lipomas are common, their occurrence in the hand is less frequent and can complicate surgical access and hand function. Giant lipomas can cause compression symptoms due to the limited space in the hand, which may lead to sequelae. Imaging studies assist us in preoperative planning and in ruling out malignant neoplasms. Complete surgical excision remains the treatment of choice, yielding good results when adjacent structures are preserved. Giant lipomas of the hand, especially in the thenar region, are rare conditions that can significantly impair hand function. Early detection and appropriate surgical treatment are essential to prevent disease progression and restore hand function.