The extension of the suprasellar subarachnoid space through an incompetent diaphragma sellae into the sella turcica is defined as empty sella syndrome (ESS). The primary form arises in the absence of previous pituitary surgery or irradiation. Predominance of obese, middle aged, often multiparous women are generally observed; clinically headaches and slight endocrine alterations are frequent but not characteristic symptoms. Rarely liquor rhinorrhea or visual campimetric defects may occur. The authors report six cases observed in their Departments of Internal Medicine during the last two years; they discuss the aspecific symptoms of presentation and the associated pathologic conditions. Standard skull X rays were negative in half the cases showing the overall poor sensitivity of this examination in detecting ESS. According to the literature no evident abnormality of hypophyseal basal hormone levels was found. Diagnosis was done by high resolution TC or MR which now must be preferred to pneumoencephalography (PEG). Three patients had peculiar pathologic conditions associated with ESS: a very high suspicion of partial insipidus diabetes was made in a man with hypo-osmolar polyuria; one patient without related humoral symptoms had a duodenal carcinoid endoscopically removed and in another primary ESS was associated with Hashimoto thyroiditis. These last two pathologies were never related before associated to primary ESS. The authors conclude that primary ESS is most often a diagnosis made by serendipity, lacking specific signs and or symptoms, whenever an imaging technique (TC or MR) is employed for detecting an unrelated endocranic pathology or the content of an enlarged sella turcica.