Introduction: Renal cell carcinoma (RCC) is one of the most common cancers worldwide. Its aggressiveness and behavior depend on different histopathological parameters, including histological types, stages, grades, etc. Objective: This study aims to observe the immunohistochemical expression of E-cadherin in renal cell carcinoma and compare it with different histopathological parameters. Methodology: This cross-sectional observational study was conducted in the Department of Pathology, Shaheed Suhrawardy Medical College, Dhaka, Bangladesh, from March 2021 to February 2023. In this study, 50 diagnosed cases of renal cell carcinoma were included. Paraffin blocks from all cases were collected, and sections were taken from each block for routine hematoxylin and eosin (H&E) staining, as well as immunohistochemical staining for the E-cadherin antibody. Relevant clinical and microscopic data, including age, sex, tumor size, histomorphologic type, and tumor grade, were collected and recorded in a predesigned data collection sheet. The statistical analysis used the spss version 26 for Windows (SPSS Inc., Chicago, Illinois, USA). The Fisher Exact test was used to analyze the association between different categorical variables. Results: 50 patients diagnosed with renal cell carcinoma were selected for the study. In this study, the age of the patients varied from 20-75 years. Most cases were in the age group 40-59 years (78%), and the mean age of the study cases was 50.86 ± 9.55 (SD) years. About 70% (n=35) of the patients were male. Most were clear cell carcinoma 29 (58%). Among the 50 cases, 20 (40%) patients were at stage pT1. Stage pT2 comprised 24 (48%) cases. Stage pT3 were found in 5 (10%) cases and stage pT4 in 1 (2%) case. Among the 50 cases, 30 (60%) patients were grade 2, grade 1 comprised 9 (18%) cases, grade 3 were found in 6 (12%) cases and grade 4 in 5 (10%) cases. E-cadherin expression was preserved in 28 (56%) cases. Statistical analysis revealed a significant association of E-cadherin with pathological staging (pT) and histological grades. However, morphological variants did not show any significant association with E-cadherin staining. Conclusion: E-cadherin expression was preserved in 56% cases of renal cell carcinoma. Loss of E-cadherin expression was significantly associated with advanced histological grades and stages of renal cell carcinoma.