Background: Our aim was to explore relevance of the proportion between neoplastic cell component and tumor-associated stroma in order to assess its association with confirmed aggressive phenotypes of right/left colon and rectum cancers in a large series of patients. Methods: The quantification of stroma component was performed in patients diagnosed with colorectal adenocarcinoma who underwent surgical resection. The analyzed variables were age, gender, anatomical/pathological features, and tumor-stroma proportion. Tumor-stroma proportion was estimated based on slides used in routine pathology for determination of T status and was described as low, with a stromal percentage ?50% or high, with a stromal percentage >50%. The tumor-stroma proportion was estimated by two observers, and the inter-observer agreement was assessed. Results: The sample included 390 colorectal adenocarcinoma patients. Stroma-rich tumors were observed in 53.3% of cases. Well-differentiated tumors had the lowest stromal proportions (p = 0.028). Stroma-poor tumors showed less depth of invasion (p<0.001). High stromal content was observed in association with tumor budding, perineural, angiolymphatic, and lymph node involvement, and distant metastasis (p?0.001). Colorectal adenocarcinoma without lymph node or distant metastasis involvement had lower stromal proportion, while metastatic ones exhibited high stromal content (p <0.001). The inter-rater reliability (concordance) between the estimations of pathologists for tumor-stroma proportions was high (?=0.746). Conclusion: The tumorstroma proportion in colorectal adenocarcinoma was associated with adverse prognostic factors, reflecting the stage of the disease. Stroma-rich tumors showed a significant correlation with advancement of the disease and its aggressiveness. Due to its availability tumor-stroma proportion evaluation has high application potential and can complement current staging system for colorectal adenocarcinoma.