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Background Prostate cancer (PCa) awareness and knowledge among men in Vhembe District, Limpopo Province, South Africa, remain inadequately studied despite the high local burden of the disease. This study investigates the knowledge, attitudes, practices, cultural beliefs, and perceived risk of PCa among men aged 40 and above in selected villages under the Mphaphuli and Niani tribal authorities. Methods A quantitative survey was conducted with 431 men, utilizing a questionnaire adapted from the African Women Awareness of Cancer (AWACAN) tool. The questionnaire, translated into Tshivenda, assessed socio-demographic data, awareness, knowledge of risk factors and symptoms, health-seeking behavior, and barriers to seeking medical help. Results The study revealed that 51.3% of participants had heard of PCa, while 48.7% had not. Awareness varied significantly with age, relationship status, education level, and language. Older men and those with higher education levels were more knowledgeable about PCa. Clinics, hospitals, and media were the primary sources of information. Misconceptions about risk factors were prevalent, with 24.0% of men indicating a preference for traditional healers for PCa symptoms. Barriers to medical help included fear of the disease, procedural fears, and cultural taboos. Multivariate analysis identified significant factors associated with PCa knowledge, including age, language, access to tap water, and cell phone ownership. Conclusion These findings underscore the importance of targeted educational interventions considering sociodemographic and cultural contexts. Future public health initiatives should focus on bridging the gap between traditional and modern medical practices to enhance health outcomes in the Vhembe District and similar settings.

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