The relationship between handedness and mathematical abilities is controversial. Whilst some researchers haveclaimed that left-handers are gifted in mathematics and strong right-handers perform the worst in mathematical tasks, it hasbeen more recently proposed that mixed-handers are actually the most disadvantaged group. To disentangle these discrepancies,we conducted five experiments in several Italian schools (total participants: N = 2,308) involving students of different ages(6 to 17 years) and a range of mathematical tasks. The results showed that (a) the percentage of variance in mathematicsscores explained by handedness was moderate (about 5%) but statistically significant, and (b) the shape of the relationshipbetween handedness and mathematical ability depended on age, task, and gender. We concluded that the different outcomesreported in the literature probably reflected the dissimilarities between the studies about the above variables. Therefore, a morecomprehensive model is needed, which explains how these variables interact.