Endoscopic ultrasound-guided biopsies have proven to be of significant value in the diagnostic evaluation of benign and malignant diseases, as well as in the staging of malignant tumours of the gastrointestinal tract and adjacent organs. The high prognostic and therapeutic relevance of the resulting cytopathological diagnoses necessitates a shared responsibility of endosonographer and cytopathologist. Quality control programs are required. The diagnostic yield of endoscopic ultrasound-guided biopsies depends on the location, size and characteristics of target tissues, and technical factors (i. e., type of needle used, biopsy technique, and material processing). Other weighing factors include training, expertise and interaction of the endosonographer with cytopathologists. On-site cytological evaluation, which has proven to be successful in optimising the diagnostic efficiency of endoscopic ultrasound-guided fine-needle aspiration biopsy, is notably practiced in Northern American and French academic institutions. It seems to be a sensible alternative to collect specimens for histological and immunohistochemical investigations in addition to the cytological smears in consideration of the economic and structural terms in the German health-care system. Endoscopic ultrasound-guided fine-needle aspiration succeeds in harvesting core biopsies in 3 out of 4 cases with 22-gauge needles. Therefore the use of 19-gauge needles for endoscopic ultrasound-guided aspiration or trucut biopsy may be necessary only in selected cases.