Erythropoietin (Epo) expression is regulated via hypoxia-inducible factor (HIF)-1alpha-directed gene transcription. Activation of the erythropoietin receptor (EpoR) by Epo leads to elevated expression of the anti-apoptotic protein, bcl-2, which has recently been shown to promote angiogenesis in malignant tumors. Expression of HIF-1alpha, Epo, EpoR, and bcl-2 was studied by immunohistochemistry in a series of 20 olfactory neuroblastoma (ONB) samples. Data were correlated with microvessel density, proliferative activity, and apoptosis in the specimens and survival analysis was performed to investigate the prognostic value of the examined factors. Immunohistochemical analysis revealed robust expression of HIF-1alpha, Epo, EpoR, and bcl-2 in ONB. Ninety percent of the samples showed HIF-1alpha immunoreactivity and in 60% of the cases, bcl-2 immunoreactivity was observed. A significant positive correlation between the expression levels of HIF-1alpha and bcl-2 and the microvessel density was found. Survival analysis did not reveal any prognostic significance for the tested factors. Expression of HIF-1alpha, Epo, Epo-R, and bcl-2 may play a functional role in ONB pathogenesis. Our data suggest that bcl-2 may act as a stimulator of angiogenesis in ONB, and thus represents a novel target for anti-angiogenic treatment strategies in the therapy of ONB.