BACKGROUND Assessment of cell proliferation activity in tumours has emerged as a common tool used by histopathologists to gain useful information for predicting the behaviour of tumours and their likelihood of local recurrence, metastatic potential, the duration of disease-free survival. It is important to demonstrate specific and sensitive techniques for determining the presence of these proliferation markers. Aims and Objectives-The purpose of this study was to evaluate the intensity, localization, and distribution of Syndecan expression in Ameloblastomas and Odontogenic Keratocysts (OKC). MATERIALS AND METHODS Total of 40 cases (20 each) of Ameloblastoma (8 Unicystic ameloblastoma & 12 Solid/multicystic ameloblastoma) and OKC was taken, and immunohistochemical staining was performed using the primary antibody for syndecan using two -step detection system based on HRP labelled polymer technique. Sample size taken for convenience. Comparison of intensity, localization, and distribution of Syndecan (CD138) between Ameloblastoma and OKC was analysed using the chi-square test/Fishers exact test. P value of < 0.05 was considered as statistically significant. Interobserver agreement was done using Kappa statics which showed score of 0.88 suggesting good agreement. RESULTS All 40 cases (20 each) of Ameloblastoma and OKC showed positivity for syndecan (CD138). OKC showed more diffuse distribution and intense staining when compared to Ameloblastoma. CONCLUSION The histologic presentation of ameloblastoma, especially unicystic type, can be, in some instances, mistaken for odontogenic keratocyst (OKC) because of their overlapping clinical and radiographic presentation. The expression of syndecan-1 in ameloblastoma showed reduced immunostaining of tumour epithelium when compared to OKC. It was also noted that the decreased expression of syndecan-1 in SMA supports the view that this variant of ameloblastoma has an aggressive biological behaviour than the UA.