Primary chest wall lymphoma is a rare condition. We report a 32-year-old woman who developed an asymptomatic right chest wall mass. Chest computed tomography (CT) showed destruction of the right 8th rib, associated with a huge extra-osseous soft tissue mass (6×5 cm) in the right chest wall. CT-guided fine needle biopsy showed diffuse, large B-cell lymphoma. The patient received 6 courses of chemotherapy with M-CHOP (methotrexate, cyclophosphamide, doxorubicin, vincristine, and prednisolone) over the course of 3 months. A Tc-99m MDP (PET CT) after chemotherapy showed no Tc-99m MDP uptake throughout her body, including the prior tumor site. After about 4 years of follow-up, chest CT-imaging revealed no tumor recurrence. In our experience, chemotherapy alone may lead to total regression of the tumor, followed by a long period of disease-free survival. Chemotherapy should be considered as the initial therapy for patients with primary chest wall lymphoma. Partial or total regression of the tumor could make surgery easier, or avoidable.