Invasive cytology of the thoracic and abdominal cavities can provide diagnostic information in a timely manner for the practitioner. The information depends on obtaining a quality sample followed by thorough cytologic evaluation. Diagnostic imaging can enhance the sampling process and minimize the risk. As an adjunct to the historic and clinical information, cytology is valuable in establishing a diagnosis or list of differentials and directing future diagnostics or therapy. The application of cytology of internal organs opens a new window for the differential diagnosis of disease.