Plasma cell-type Castleman disease (PCD) is often encountered when differentiating IgG4-related disease (IgG4-RD). Given that serum IgA is often elevated in Castleman disease, we investigated whether IgA expression levels in histological specimens can be used to differentiate between the two diseases. Lymph node lesions obtained from 12 IgG4-RD and 11 PCD patients were analysed by immunohistochemistry with anti-IgG, -IgG4, and -IgA antibodies. In addition to all 12 cases of IgG4-RD, 8/11 cases (72.7 %) of PCD also met the diagnostic criteria of IgG4-RD (serum IgG4135 mg/dl and IgG4/IgG-positive cells40 %). IgA-positive cells were sparsely and densely distributed in IgG4-RD and PCD cases, respectively. The median number of IgA-positive cells +/- SD in all 12 cases of IgG4-RD was 31 +/- 37 cells per three high-powered fields (3HPFs) (range 4-118 cells/3HPFs). In contrast, the median number of IgA-positive cells, which was significantly higher in all 11 cases of PCD, was 303 +/- 238 cells/3HPFs (range 74-737 cells/3HPFs) (P < 0.001). In conclusion, our findings indicate that in cases where serum analysis-based data are unavailable, anti-IgA immunostaining can be used for differential diagnosis of IgG4-RD.