BACKGROUND Melanoma is a malignant transformation of melanocytes known for its capacity to metastasize, necessitating early diagnosis and intervention. While over 97% of melanomas are diagnosed with a known primary site, such as the skin, eye, or mucous membranes, rare cases like melanoma of unknown primary (MUP) can present with atypical manifestations, highlighting the need for comprehensive examinations. CASE REPORT In January 2023, a 68-year-old woman presented with a 4-week history of swelling and discoloration in her left upper eyelid, revealing a hard, livid mass indicative of malignancy. Surgery and subsequent histopathology confirmed epithelioid cell melanoma in the lacrimal gland. Although no other primary melanoma sites were found, imaging and biopsy in August 2023 identified metastatic spread to her lungs. Despite proton radiotherapy, progression led to thoracoscopic surgery for metastasis resection in September 2023. Further re-evaluation revealed metastases in both lungs, leading to her enrolment in a trial comparing PD-1 (programmed death ligand 1) antibody plus LAG-3 (lymphocyte activation gene 3) antibody with PD-1 monotherapy. Subsequent progression required treatment with ipilimumab and nivolumab, which resulted in near complete regression of the orbital tumor. Unfortunately, she later developed serious complications, including hypophysitis, lung infection, renal failure, and viral meningitis, which ultimately led to her death in April 2024. CONCLUSIONS This case report highlights the diagnostic challenge in distinguishing between melanoma of known and unknown primary origins. It emphasizes the importance of thorough histological work-up and heightened suspicion for melanoma of the lacrimal gland, despite its rarity, to ensure prompt diagnosis and treatment due to its metastatic potential.