Molecular cytogenetic techniques have shown that most parathyroid adenomas are monoclonal, i.e., are true neoplasms. But even though such neoplasms may be of single-cell origin, monoclonal tumors apparently can develop from polyclonal lesions, histologically displaying a hyperplastic pattern. The histopathological diagnosis is crucial for determining the necessary scale of the surgical procedure. In routine parathyroid pathology, conventional histological examinations, including intracellular fat staining of parenchymal cells, are still the most valuable diagnostic tools. Since it is sometimes difficult to distinguish benign from malignant tumors, the only reliable carcinoma criteria are infiltrative growth or the presence of metastases. As it can be difficult or even impossible to distinguish adenomas from carcinomas in frozen sections peroperatively, paraffin-embedded sections are often required in order to corroborate the histopathological diagnosis. Carcinoma cells often show greater cellular and nuclear uniformity than do the pleomorphic cells seen in some adenomas. Mitotic activity is more obvious in carcinomas than in adenomas, but there are exceptions. In modern parathyroid pathology, immunocytochemical methods and DNA determination may be integrated as tools into the routine diagnostic examination. The use of proliferation markers has attracted increasing interest and DNA determination may also be of value, not least to assess the growth potential of parathyroid tumors. However, it remains to be seen what role the application of molecular and genetic techniques will play in improving and further developing diagnostics in parathyroid pathology.