The appearance of malignant cells in body fluids like urine, blood or body-cavity fluids are a clear indication for the existence of a tumor and urine or body-cavity fluid cytology are routine diagnostics today. Cytologic examination of the cellular features of fluids is a valuable adjunct to patient diagnosis and the staging and management of tumors. The German-language literature contains the earliest references to the cytology of malignant cells in fluid specimens. Preparation of the specimen has evolved from unstained wet smears to protocols that generally include centrifugation and the generation of stained smears and a cell block. The smears may be alcohol-fixed direct smears, cytospins, or a liquid-based preparation, and they are usually stained with the Papanicolaou method. Additional techniques, such as immunocytochemistry and flow cytometry, provide significant help in this differential diagnosis. Evaluation of microscopic images after Papanicolaou staining eluded digital pathology, an image-based information environment enabled by computer technology that allows for extracting information from a digital slide. With the advent of full-slide scanning digital methods are regarded as promising way to achieve better, faster and cheaper diagnosis, prognosis and prediction of cancer and other important diseases. One important feature are combinations with immunostaining, FISH technology etc., to elude additional information from the specimen. Circulating tumor cells (CTCs) can be found in the bloodstream and are always ready to attach to endothelial cells lining blood vessels and extravasate to enter tissues and organs to form a metastatic site. They show plastic phenotype and a small number of these cells undergo the epithelial-to-mesenchymal (EMT) program. De-differentiation and dissemination from the primary tumor is a basic prerequisite for colonization and growth of distant metastasis. Phenotypic and functional plasticity of cancer cells and the ability to adapt permanently to demanding conditions provide great challenge for identification and characterization of CTC´s from bloo