This study aimed to investigate the effects of both sodium fluoride (NaF) and 7,12-dimethylbenz[a]anthracene (DMBA), both separately and in combination, on some blood parameters and hepatic, renal, and cardiac histopathology in rats. Forty male Wistar albino rats, weighing 250–300 g, were randomly divided into one control and three experimental groups (i) a NaF group who received 15 ppm of NaF in their drinking water for 90 days, (ii) a DMBA group who received 10 mg DMBA/kg body weight/po/weekly for 90 days, and (iii) a NaF+DMBA group who received 15 ppm NaF in their drinking water plus 10 mg DMBA/kg bw/po/weekly for 90 days. The animals in the groups were sacrificed at the end of the 90 days. The AST, ALT, LDH, CK, creatinine, troponin I, and MDA levels increased in the NaF, DMBA, and NaF+DMBA groups compared to the control group, while the WBC, K, Na, Cl, urea, SOD, GSH-Px, CAT, and GSH values showed a statistically significant decrease (p<0.05). In addition, the CK-MB significantly increased in the DMBA and NaF+DMBA groups compared to the control group (p<0.05). The histological structure of the liver, kidney, and heart tissues in the control group was normal. In the NaF and DMBA groups, degenerative and necrotic changes were detected. In the NaF+DMBA group: (i) the liver exhibited hydropic degeneration and coagulation necrosis in hepatocytes, severe dilation in the sinusoids, congestion in the central and portal regions, and mononuclear cell infiltration in the portal region; (ii) the kidneys displayed congestion in the glomerulus and interstitial vessels, interstitial nephritis, diffuse hydropic degeneration, and coagulation necrosis in the tubule epithelium; (iii) the heart showed myocardial hyperemia, severe mononuclear cell infiltration in interstitial tissue, hyaline degeneration, and Zenker’s necrosis in myocardium As a result of these blood and oxidative stress parameters and histopathological findings, it was determined that NaF, DMBA, and NaF+DMBA induce toxicity in the liver, kidney, and heart tissues and thus play an important role in the physiopathology of toxicity.