To determine the prevalence of neuroendocrine differentiation in human thymic neoplasms, which are unusual tumours that may range from well-differentiated to overtly malignant, poorly differentiated lesions, an immunohistochemical study was conducted in 23 thymic neoplasms re-classified on the basis of the new 1999 WHO classification. Immunohistochemical evidence of neuroendocrine differentiation in the form of reactivity to the markers synaptophysin, neuron-specific enolase and chromogranin A was found in 6 of 23 tissues (26%). Two of 3 patients with thymic carcinoids (or well-differentiated thymic neuroendocrine carcinoma) were affected by multiple endocrine neoplasia type 1 (MEN-1). Myasthenia gravis was present in 2/6 patients with neuroendocrine differentiation. This study demonstrates the high prevalence of neuroendocrine markers in human thymic neoplasms. Whether and in what percentage of cases immunohistochemical reactivity may be correlated with clinical behaviour and outcome remains a controversial issue. Finally, the association between thymic carcinoids and MEN-1 is a strong indication for clinical and possibly genetic screening of all patients presenting this feature, just as all MEN-1 patients have to undergo thoracic imaging and prophylactic thymectomy in selected cases.