Objective: CXC chemokines enhance tumor cell survival and proliferation. Especially CXCR4 promotes tumor development by stimulating angiogenesis and favoring metastasis. In contrast, CXCR3 is angiostatic and may exert an anti-tumor effect. Since tumor budding is linked to vascular/lymphatic invasion and lymph node (LN) and/or distant metastasis in colorectal cancer (CRC), here we explored the expression of CXCR3+4 in relation to tumor budding. Method: A multiple-punch tissue microarray of 220 CRCs with full clinicopathological information including therapy underwent immunohistochemistry for CXCR3 and CXCR4. Expression was evaluated in tumor-center, -front and -buds and correlated to clinical data. Results: CXCR3-expression was homogeneous throughout tumor-center, -front and -buds (average 40 %) and was unrelated to clinicopathological features or survival. CXCR4-expression was high in tumor-center and -front but reduced (p<0.001) in buds (76 %, 77 %, and 20 %, respectively). Maintenace of CXCR4-expression within buds was predictive of LN-positivity (p<0.0001) and lymphatic invasion (p<0.0001) but not of venous invasion or distant metastasis. CXCR4-positivity in buds was associated to poor outcome (p=0.0048) in LN-negative CRCs (p=0.0191). Conclusion: Maintenance of CXCR4-expression in buds has a profound effect on tumor aggressiveness and prognosis in LN-negative CRC-patients. This would help in establishing a tumor budding "profile" especially linked to LNmetastasis in CRC. Objective: COX-2 expression was investigated in colorectal cancer and colorectal precancerous lesions. Its expression in adenomas is associated with increasing size and neoplastic potential. Little is known about COX-2 expression in subtypes of serrated colonic polyps, which constitute substantial number of colon cancer precursors. The aim of the study was to assess COX-2 expression in serrated polyps of the colon and to investigate its potential discriminative role. Method: 175 consecutive serrated polyps were analyzed. They included: 26 traditional serrated adenomas (TSA), 36 sessile serrated polyps (SSP) and 113 hyperplastic polyps (HP). COX-2 expression was assessed semi-quantitatively (0-3). Kruskall-Wallis test was used for the comparison of COX-2 expression between serrated categories (α=0.05). Objective: In colorectal cancer (CRC), tumor buds represent a more aggressive tumor cell type at the invasive front with apparently low proliferation. The aim of this study was to determine the proliferation potential of tumor buds by comparing Ki67 staining across different tumor areas and adjacent normal tissue. Method: Whole tissue sections from 197 patients with CRC underwent immunohistochemistry for Ki67. 10 high-powerfields were evaluated for each of the following regions: normal mucosa, tumor center, tumor front and tumor buds. Ki67-positivity was correlated to patient outcome. Results: Average Ki67-positivity was 5.2 % in normal mucosa and significantly higher in the tumor center (38.2 %; p < 0.0001) and invasion front (34.9 %; p < 0.0001). Strikingly, only 0.3 % of all tumor buds showed Ki67-positivity (p<0.0001). Although Ki67-positivity in the tumor center or front was unassociated with clinicopathological features or patient survival, the greater the number of Ki67-positive tumor buds, the worse the prognosis. This effect was also found after adjusting from TNM stage (HR (95 % CI): 2.25 (1.1-4.5); p=0.0193)). Conclusion: A marked absence of Ki67 staining is found in most tumor buds, suggesting a substantially decreased proliferation rate. However, the association of Ki67-positivity with worse prognosis in 15 % of cases points towards a heterogeneous population of tumor buds.