Several interleukin (IL)‐10 producing B‐cell subsets have been identified recently. However, few studies have examined the role of them in toxic epidermal necrolysis (TEN). We describe a 41‐year‐old woman with TEN who had B‐cell lymphoma and a history of treatments including B‐cell depletion therapy. Her re‐epithelization was still ongoing after 7 months, despite treatments. To investigate her immune system, we compared cytokine and chemokine production from B cells and non‐B cells isolated from the patient and another non‐lymphoma TEN patient. IL‐10 production from B cells decreased in the patient compared with the control TEN‐only patient. Cytokine and chemokine levels from non‐B cells involved in inflammation were elevated in the patient compared with the control patient. In conclusion, this study demonstrates that IL‐10 from B cells as well as regulatory T cells is critical in the pathogenesis of TEN, and that B‐cell dysfunction based on B‐cell lymphoma and B‐cell depletion therapy may be involved in the intractability of TEN.