Internistic pathology is a relatively new term that covers a part of the pathology which deals with the histopathologic diagnosis of predominantly non-tumor conditions, and to a lesser extent of the tumor, inside the various branches of internal medicine, such as pulmonology, hematology, nephrology, gastroenterology, dermatology and immunology. After examination of the morphological changes of diseased tissue the pathologist designates diagnosis that is worked out with additional clinical data. However, a pathologist often sets the definitive diagnosis immediately that determines the further course of the patient’s treatment. Internistic pathology includes a complex and sophisticated system of diagnostics in pathology that implements basic pathohistological diagnostics integrated with histochemical, immunohistochemical, immunofluorescence and molecular techniques as well as electron microscopic analysis. Paucity of tissue obtained mainly during various endoscopic procedures and through the needle biopsy is one of the peculiarities of this pathological branch. Interpretation of changes in the analyzed cells and tissues is often limited by the availability of clinical data on the patient’s condition and the correlation of morphological changes with the clinical data is necessary to complete the diagnosis properly. From the above it can be concluded that from the diagnostic point of view the internistic pathology is very demanding and challenging branch of pathology that uses the most recent tools to acquire the knowledge of pathological substrate of disease for known as well as for unknown clinical entities. Key words: biopsy; diagnosis; internal medicine; microscopy; pathology