Giant-cell carcinoma of the lung (GCCL) is a rare histological form of poorly differentiated non-small-cell lung cancer, which is classified as a subtype of pulmonary sarcomatoid carcinomas. In this case report, we describe the case of a 57 year old female with a past medical history of HIV on HAART (CD4 count at the time was 621 cell/μl). She presented to the hospital with a two months history of productive cough with yellowish sputum containing streaks of blood, twelve pound weight loss, bilateral hand swelling, and knee pain with noticeable finger clubbing on physical examination. Chest computed tomography scan and subsequent bronchoscopy was performed and revealed a protruding endobronchial lesion in the right upper lobe (RUL) bronchus. Definitive diagnosis established by way of pathologic analysis of the resected specimen obtained from RUL lobectomy revealed sarcomatoid giant cell carcinoma, with tumor size 9.5 cm and invasion of the visceral pleura and 1/13 hilar lymph node involvement. The pathological stage was determined as pT3N1Mx based on the tumor node metastasis (TNM) staging system. The patient was started on adjuvant combination cisplatin and docetaxel therapy with supplemental G-CSF four months after surgery and followed as an outpatient. The significance of this case is that it highlights a very rare lung cancer, unveiling a possible paraneoplastic syndrome associated with this malignancy and the impact of HIV HAART therapy in carcinogenesis.