Background: The relative frequency of malignant tumors has been reported to have an association with age, gender, and location. The current study is a retrospective study to assess the pattern and relative frequency of different malignant tumors in Najran, Saudi Arabia. Methods and Results: All patients from both genders were included in the study from June 2014 to May 2019, and data were retrieved from the records of confirmed cancer cases at the departments of pathology. For 5 years, a total of 763 cases [325(42.6%) men and 438(57.4%) women] and 37 types of malignant tumors were diagnosed in Najran. According to the histopathological diagnosis, carcinomas were the most frequent tumors (n=564, 73.9%). According to the affected organ/body system, tumors of the gastrointestinal system were the commonest malignancy, observed in 156 (20.4%) of the patients (91 men and 65 women). Finally, the chi-square test revealed that the frequency of malignant tumors climbed as age increased (P=0.0005). Conclusion: The relative frequency of several cancers in Najran showed that the most common cancers in both genders are in the following order: gastrointestinal, thyroid, breast, skin and soft tissue cancers, and lymphoma. In addition, women are more affected than men, and increasing age is a risk factor to develop a malignancy.