A 73-year-old man presented with multiple lymphadenopathy. He had a 20-year history of palmoplantar psoriasis evolved to a diffuse erythrodermic picture in the last two years. Topic and systemic medications including prednisolone, acitretin, anti-IL17 (ixekizumab), TNF inhibitor (adalimumab), anti-IL23 (guselkumab), methotrexate, cyclosporine, and phosphodiesterase 4 inhibitor (apremilast) were ineffective. Repeated skin biopsies excluded mycosis fungoides, confirming psoriasis; molecular analysis of T-cell receptor genes ruled out clonality. The axillary lymph node histology documented a dermatopathic lymphadenitis, often associated with chronic cutaneous inflammatory diseases. At an accurate morphological evaluation, features of HHV8-positive multicentric Castleman disease were observed. Moreover, in a few follicles, in situ mantle cell neoplasia was identified. The translocation t(11;14)(q13;q32), characteristic of mantle cell lymphoma, and the monoclonal IGH gene rearrangement were present. HHV8 DNA was identified on plasma sample. Multicentric Castleman disease in psoriatic patients is a rare event and it might be favored by the immunomodulatory treatment in longstanding psoriasis. Multicentric Castleman disease patients are predisposed to developing simultaneous or subsequent lymphoma. In situ mantle cell neoplasia often behaves indolently, although it may progress to overt mantle cell lymphoma. Rituximab achieved a good control of psoriasis. Unfortunately, the patient developed Staphylococcus aureus sepsis for which he is currently on antibiotic therapy.