Oral lesions that are associated with human immunodeficiency virus (HIV) infection are often the first clinical signs of an underlying infection. This study aimed to test primary healthcare (PHC) nurses’ knowledge and practices before and after an educational intervention on the detection and management of oral diseases, and in particular, those associated with HIV infection. A crosssectional study was conducted among PHC nurses who were employed in a range of clinical settings within the public sector (hospitals, clinics and nurse training colleges) in urban and rural areas in the uMgungundlovu Health District of KwaZulu-Natal. The convenience sample comprised 121 nurses who completed a self-administered questionnaire, undertook pre-education testing, were provided with educational material and underwent post-education testing. The obtained results showed that most nurses (90%) had received little or no undergraduate or postgraduate training in the examination, diagnosis or treatment of oral lesions. Analysis of the pre-education test results that pertained to the identification of a number of oral lesions revealed a mean correct response rate of 38.5%. Post-education results revealed a statistically significant (p-value < .0001) (24%) improvement to 62.4%. The provision of a basic education intervention can have significant effects on knowledge, treatment and referral patterns, and can lead to early diagnosis, treatment and improved quality of life for persons who are infected with HIV.