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Objectives: This study aimed to investigate the expressions of p53 and ki67 genes in the characterization of leiomyomas. Materials: Fifty (50) Paraffin embedded tissue blocks were selected from the department of Histopathology, Niger Delta University Teaching Hospital, Okolobri from January 2011 to August 2019. The histological characterization and morphological evaluation were defined using the routine Hematoxylin and Eosin staining method. Immunostaining was done for p53 and ki67 using the manufacturers antibodies. Results: A direct correlation between age and the expression of the p53 gene was also made in this study. It was observed that in patients within the ages of 50-59 and 60-69, there was markedly no expression of the p53 gene whereas in patients within the ages of 20-29, there was still some level of expression (20%) and ages 30-39 (80%) and finally 40-49 (10%). There was no expression (0.0%) of Ki-67 in uterine leiomyomas across all age groups. Conclusion; This study therefore has suggested that based on the percentage of expression, it can rightly be inferred that the p53 gene is a good indicator in the immune-histochemical characterization of leiomyomas as it has good sensitivity and good prognosis as opposed to Ki67.