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Objective To investigate the clinicopathological characteristics of esophageal squamous intraepithelial neoplasia (ESIN), and to accurately differentiate between the“cell atypia”and“tissue atypia”, aiming to provide a theoretical basis for accurate diagnosis of ESCI for clinical pathologists. Methods Clinical data of 162 patients with typical ESIN were collected. Typical manifestations of ESIN were observed under light microscope. Clinicopathological features indicative of the neoplasia were summarized, and the pathological causes of the neoplasia were analyzed. Literature review was also conducted. Results The male-to-female ratio was 126 ∶ 36 and the average age was (61.48±9.16) years. In the age grouping, Mann-Whitney test showed that the differences in the median ESIN grade among different age groups were statistically significant (Z = -2.911, P = 0.0036) . Compared with the < 61-year- old group, ESIN was more likely to occur in the ≥ 61-year-old group. Light microscopy revealed clinicopathological features indicative of neoplasia, such as increased nuclear-cytoplasmic ratio, increased mitotic figures, more keratinized granules and nucleated cells in the surface layer, eosinophilic cytoplasm of tumor cells, sebaceous gland-like cells in the basal layer, neoplastic cells growing in parallel or obliquely, disordered cell arrangement and absence of polarization, absence of maturation gradient, abnormal keratosis, intraepithelial angiogenesis and epithelial foot extension or push-type growth. Conclusions ESIN is more likely to occur in men aged 61 years or older. Light microscopy reveals potential clinicopathological features indicative of neoplasia, which can assist clinical pathologists to make accurate diagnosis of ESIN. [ABSTRACT FROM AUTHOR]