Until now pituitary tumors are considered as benign and usually named ‘‘pituitary adenomas’’, whereas only the very rare pituitary tumors (0.2%) with subarachnoid, brain or systemic metastasis are considered as malignant, the so-called ‘‘pituitary carcinomas’’. However, it is well known that a certain number of pituitary ‘‘adenomas’’ are capable of aggressive growth and invasion of the surrounding structures and recurrence. The 2004 edition of the ‘‘World Health Organization (WHO) classification of tumors of endocrine organs’’ [2] reflects the progress that has been achieved since the previous edition [3]. Some major advances have been made regarding the identification of transcription factors that regulate cell differentiation, and hormonal activity of adenohypophysial cells on the one hand, and the role of putative oncogenes and tumor suppressor genes, and growth factors implicated in pituitary tumorigenesis, on the other. However, we are still lacking well-defined prognostic factors or criteria of malignancy other than metastasis, although some are promising, such as the expression of polysialylated NCAM (PSA-NCAM). We have established a clear relationship between PSA-NCAM expression, invasion and metastasis in transplantable pituitary tumors in rats that represented malignant and benign lineages [1], which was confirmed in human pituitary tumors [8]. In the 2004 WHO classification, pituitary adenomas remain classified on the basis of their hormonal secretion, immunoprofiles and ultrastructural characteristics. In our opinion, the latter technique is not yet helpful and some ultrastructural types are confusing. Although one chapter is dedicated to the rare pituitary carcinoma [7], only one paragraph in the introductory chapter [5] deals with ‘‘atypical adenomas’’, which are defined by the following histological features: ‘‘an elevated mitotic index and a Ki-67 labeling index greater than 3%, as well as extensive nuclear staining for p53 immunoreactivity. These features are usually lacking in non-invasive adenomas and present in nearly all pituitary carcinomas’’. Based on these very similar histological features the following question arises: are ‘‘atypical adenomas’’ true pituitary carcinomas without metastases? Moreover, it is well known that many (around 50%) adenomas of each type are able to invade the surrounding tissues (dura, sphenoidal and cavernous sinus, bone). These tumors are named ‘‘invasive adenomas’’ and are considered as benign. This is in contradiction with the definition of a benign tumor, but it is based on rare studies showing that invasive adenomas did not recur more often than non-invasive ones [6]. It remains that even in true pituitary carcinoma, as in other endocrine tumors, the histological features of malignancy are discrete. The histological proof of invasion is only in exceptional cases at the disposal of the pathologist, and the MRI criteria of invasion controversial. Moreover, it is often difficult to differentiate a stable post-operative remnant from a true recurrence. Therefore, to evaluate the prognostic value of previously published markers, we need to correlate them with well-defined criteria of invasion (MRI and/or histological), growth rate and clinical follow-up in large cohorts of patients exhibiting tumors of aggressive behavior. This needs a collaboration between pathologists, neurosurgeons, radiologists and endocrinologists. It is likely that we will find new prognostic markers by new technologies, such as gene expression analysis by microarrays, but only if these techniques are performed in well-characterized subgroups of tumors. A prognostic classification or a grading based on radiological or histological signs of invasion, hormonal status (silent D. Figarella-Branger (&) Service d’Anatomie Pathologique et de Neuropathologie et Laboratoire de Biopathologie de l’Adhesion et de la Signalisation, EA3281, Faculte de Medecine timone, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France E-mail: dominique.figarella-branger@medecine.univ-mrs.fr