The recognition of early invasion in endocervical adenocarcinomas can be difficult. We evaluated the proximity of endocervical glands and their pattern of infiltration in relation to thick-wall blood vessels as potential markers of invasion in a series of invasive endocervical adenocarcinomas removed by cone biopsy or hysterectomy. Routinely stained slides were examined from 50 invasive endocervical adenocarcinomas (37 of usual type and 13 of minimal deviation type), 26 noninvasive lesions (14 cases of adenocarcinoma in situ, 7 cases of hyperplasia, 4 cases of tunnel clusters, 1 adenomyoma), and 20 normal cervices, including 7 with deep nabothian cysts. The range of vessel wall thickness using an ocular micrometer was recorded in each specimen. A blood vessel with a wall > or =36-microm thick was defined as thick-walled. Both the blood vessel wall thickness and distance to the closest gland was recorded for each case. The median distance from a thick-wall blood vessel to a gland in the invasive tumors was 30 microm compared with 168 microm in the noninvasive group. In both groups, the measured blood vessel wall had a median thickness of 42 microm. The pattern of infiltration of glands around the thick-wall vessels was classified as "circumferential," in which multiple glands circumferentially enveloped the vessel, or "molded," in which single or multiple distorted glands were molded around the vessel. The circumferential and molded patterns were identified in 35 (70%) and 10 (20%) of 50 invasive adenocarcinomas, respectively. Of the 26 lesions in the noninvasive group, only 3 (6%) had a circumferential pattern and none had a molded pattern. Importantly, none of the cases in the noninvasive group showed either pattern in the presence of glandular atypia. In conclusion, close proximity of glands to thick-wall blood vessels (distance from the closest gland to a thick-wall vessel less than or equal to the thickness of the vessel wall) seems to be a useful feature in the diagnosis of invasive endocervical adenocarcinoma. This feature, in combination with certain glandular growth patterns and cytologic atypia, can be highly suggestive, if not diagnostic, of invasive carcinoma.