Rationale: Diffuse large B-cell lymphoma (DLBCL) is a neoplasm of large B lymphoid cells that exhibits diffuse growth patterns. Patients may present with nodal and/or extranodal disease. The most common extranodal site is the gastrointestinal tract, while skin is less common.

Patient concerns: We report a case of secondary skin involvement of an original gastric DLBCL, which has achieved a complete response after treatment with chidamide.

Diagnoses: Initially, the diagnosis of gastric DLBCL is clear, and this patient responded well to systemic chemotherapy (rituximab + cyclophosphamide + epirubicin + vincristine + prednisone) after 8 cycles. Thirty months later, some rapidly enlarging skin nodules on his arm were found. These skin nodules were diagnosed as secondary cutaneous DLBCL based on the clinical features, positron emission tomography-computed tomography, and histomorphologic and immunohistochemical expression.

Interventions: Steroids, interferon-α, and radiation had little therapeutic effect. We treated the patient with chidamide at 30 mg twice per week in combination with dexamethasone.

Outcomes: The skin nodules regressed 3 weeks later. During the 1-year follow-up period, the patient is still in treatment with chidamide without adverse reactions.

Lessons: To the best of our knowledge, this is the first case of secondary skin DLBCL reported to exhibit a complete response to chidamide, which provides a novel therapeutic strategy for secondary skin DLBCL. However, more cases are still needed to further validate its efficacy.