The objective of this study was to investigate nucleophosmin/B23 (NPM) expression in renal cell carcinomas (RCC) and renal oncocytomas. The expression of NPM was studied by immunohistochemical methods on 59 RCCs, 9 oncocytomas, and 19 tumour-negative renal tissues. The expression was assessed relative to various clinicopathological variables and histological subtypes, to determine its potential role as a prognostic and diagnostic marker. All tumours showed nuclear staining, and a minority also exhibited cytoplasmic immunoreactivity. Two patterns of nuclear staining were observed: nuclear staining with a prominent nucleolus (nucleolar staining) and nuclear staining without a prominent nucleolus. There were significant differences, in both nuclear staining and cytoplasmic NPM expression, between oncocytomas and chromophobe RCCs (p<0.001) and clear cell RCCs (p<0.001). Cytoplasmic NPM expression was markedly lower in RCCs than in oncocytomas. A statistically significant correlation was discovered between nucleolar staining and nuclear grade (p<0.001, r=0.5). No relationship was found between cytoplasmic expression of NPM and any of the clinicopathological parameters or survival. NPM might be a useful immunohistochemical marker for differential diagnosis between oncocytoma and chromophobe RCC. In addition, increased nucleolar NPM expression in RCCs appears to be associated with tumour progression. © 2011 The Authors. APMIS © 2011 APMIS.