Approximately 42% of the Sudanese population use toombak as smokeless tobacco. Tobacco specific N-nitroso compounds have been detected at high concentration in toombak. This study focused on the possible carcinogenicity of those compounds through the measurement of serum CEA and serum AFP in both toombak users and smokers. 160 subjects were involved with the average age of 32 years ranging from 20 to 60 years. These 160 subjects were categorized into 3 groups (control, smokers, and toombak users). Serum CEA and AFP were measured using an IRMA technique. The mean AFP level in the control, toombak users and smokers groups were 0.94, 1.98 and 2.34 Ku/l respectively. There is a significant difference between the means of serum AFP level in both smokers and toombak users and control group, p = 0.0045 and p = 0.0049 respectively. 13.2 % of the toombak users and 23.5 % of smokers have had serum AFP levels more than the upper limit of the normal range (0-3.28 Ku/l). Serum CEA level in control group ranged from 0 to 5.28 µg/l. The mean serum CEA levels of the toombak users and smokers was not differ significantly from that of the control group (p > 0.05). But 12.7% of the Toombak users and 14.7 of the smokers have had CEA level more than the upper limit of that of control. The relation between the duration of smoking and the level of CEA and AFP as well as the effect of age of subjects on the level of these analyte were studied. The results show no significant correlations where p > 0.05.