High plasma lipoprotein (a) [Lp(a)] concentrations are an independent risk factor for atherosclerotic diseases. To date, no effective intervention strategies on reducing Lp(a) concentrations have been reported. The aim of the study was to evaluate the possible modulation of two polymorphisms of LPA gene (LPA 93C>T and LPA 121G>A) and nutritional habits on Lp(a) concentrations. We studied 647 healthy Italian subjects (260 M; 387 F) with a median age of 48 years (range: 19-78) enrolled in an epidemiological study conducted in Florence, Italy. A linear regression analysis showed a significant negative influence of fish intake (beta=-0.174+/-0.084; p=0.04) on Lp(a) concentrations, after adjustment for smoking habit, C-reactive protein serum concentrations, dietary habits and LDL-cholesterol concentrations. With regard to LPA polymorphisms, LPA 93C>T polymorphism resulted to significantly affect Lp(a) circulating concentrations in a dose-dependent manner, with lower concentrations shown by subjects carrying the T rare allele, whereas no significant influence of LPA 121G>A polymorphism on Lp(a) concentrations was observed. Moreover, by analyzing the possible interplay between LPA 93C>T and dietary fish intake, a significant interaction between these two determinants in lowering Lp(a) concentrations was reported. In addition, lower Lp(a) concentrations were observed in subjects carrying the T allele of the LPA 93C>T polymorphism and consuming a high intake of fish with respect to those being in the highest tertile of fish consumption but homozygotes for the common allele of the polymorphism. In conclusion, this study reported a significant interaction of daily fish intake and LPA 93C>T polymorphism in decreasing Lp(a) concentrations.