Tuberculosis (TB) of the rib is a very rare form of skeletal TB and its diagnosis may be difficult because of a low index of suspicion by clinicians. The presentation often mimics malignant disease clinically and radiologically and diagnosis may only be confirmed by tissue biopsy. We present a 32-year-old HIV-negative man who presented with a three-month history of progressively worsening pleuritic chest pain, weight loss, fatigue, anorexia and low-grade fever with night sweats. A chest computerized tomography (CT) scan showed destructive lesions in the right fourth and seventh ribs with no pulmonary lesions. A diagnosis of TB of the rib was made after surgical resection and histopathology of the affected tissue. There was significant improvement when anti-TB therapy was initiated. This case report emphasizes the importance of a high index of suspicion of TB in patients presenting with destructive bone lesions in regions with high prevalence of TB.