An important role in the differentiation of tissues in different organs is played by transforming factors (TFs); pancreatic and duodenal homebox 1 (PDX-1) is one of the earliest factors for pancreatic cells. Many malignant tumors, including neuroendocrine tumors (NETs), are similar in structure, and therefore the actual problem of oncomorphology is to search for narrow-specific markers and TFs. Objective: to comparatively analyze and assess the value of the expression of the TF PDX-1 in NETs and non-NETs of different localization and histogenetic origin. Material and methods. Anti-PDX-1 antibodies were used to study 528 tumors divided into 3 groups: Group 1 included 394 NETs, among them there were those of the pancreas (n=173), stomach (n=46), bowel (n=65), lung (n=40), thymus (n=8), kidney (n=6), Merkel’s cell carcinomas (n=14), NETs of the breast (n=3), larynx (n=2), trachea (n=2), bladder (n=1), and metastatic NETs (n=34) of unknown primary site; Group 2 consisted of 16 tumors, of them there were paragangliomas (n=6), medullary thyroid cancers (MTC) (n=6) and adrenal pheochromocytomas (APCC) (n=4); Group 3 comprised 118 non-NETs, among them there were tumors of the pancreas (n=54), stomach (n=26), bowel (n=17), lung (n=11), breast (n=3), kidney (n=4), adrenal glands (n=2), and bladder (n=1). Results. PDX-1 was positive in 75.1% (130/173) of pancreatic NETs, all insulinomas (50/50), gastrinomas (11/11), somatostatinomas (3/3), ACTH-producing tumors (2/2); PDX-1 was positive in the non-functioning pancreatic NETs, all PPomas (19/19), 76.1% (35/46) of NETs without the hormone detected, 50% (2/4) of calcitoninomas, and 21.1% (8/38) of silent glucagonomas. PDX-1 was positive in 32.4% (11/34) of carcinoids and 50% (6/12) of neuroendocrine carcinomas, all duodenal NETs (18/18), 90% (9/10) of rectal carcinoids and 30.8% (4/13) colonic carcinoids, 37.5% (3/8) of thymic/mediastinal carcinoids, 66.7% (4/6) of kidney carcinoids, and 37.5% (9/24) of metastatic NETs of unknown primary site. PDX-1 was negative in all carcinoids of the colon and sigmoid (0/5), ileum and jejunum (0/24), lung (0/40), trachea (0/2), larynx (0/2), Merkel’s cell carcinoma (0/14), breast (0/3), bladder (0/1), as well as MTC (0/6), APCC (0/4), and paragangliomas (0/6). PDX-1-positive non-NETs included 81.8% (18/22) of adenocarcinomas (AC) and all serous cystic, mucinous cystic, intraductal and acinar cell tumors of the pancreas (4/4, 3/3, 2/2, and 3/3), 57.1% of AC (8/14) and 83.3% of signet ring cell carcinomas of the stomach (10/12), 56.2% AC of the bowel (9/17), bladder cancer (1/1). PDX-1 was negative in all anaplastic cancers (0/2) and solid pseudopapillary tumors of the pancreas (0/20), cancers of the lung (0/11), kidney (0/4), breast (0/3), and adrenal glands (0/2). Conclusion. The expression of PDX-1 is very specific for most digestive tract NETs and non-NETs. Pancreatic ductal and acinar cell tumors and gastric signet ring cell carcinomas are most commonly PDX-1-positive. Most tumors that do not originate from the digestive tract have a PDX-1 negative immunophenotype.