Colorectal cancer (CRC) represents a significant global health problem. Finding the biomarkers is crucial for the diagnosis and prognosis prediction. CD44 is a cancer stem cell (CSC) marker that plays an important role in tumor cell proliferation, adhesion, migration, and invasion. Altered mucin expression has been observed in cancer cells and also affects their biologic properties. This study aimed to analyze CD44 expression, assess acidic mucin histochemical alterations in CRC cases and to find the relation between both. A total of 40 colectomy specimens were included. Sections from formalin-fixed paraffin embedded blocks of the tumors were stained immunohistochemically with anti-CD44 antibodies and histochemically using Alcian Blue (AB) at pH 2.5. AB staining was positive in 26 (65%) cases including all mucinous carcinoma cases. It was significantly related to tumor histology (P= 0.000), lymph node status (P=0.000) and TNM staging groups (P= 0.000). CD44 expression was positive in 30 (75%) cases. Positive cases were scored as +1, +2 and +3. CD44 expression was significantly related to lymph node status (P= 0.001) and TNM staging groups (P= 0.006).  There was a significant relationship between CD44 expression and AB staining (P = 0.006) with a moderate negative correlation (r= -0.424). Increased CD44 expression and decreased acidic mucin correspond with lymph node metastasis and higher stage in CRC cases, suggesting both as indicators of worse prognosis.