Objective: Increased rates of atypical handedness are observed in groups of neurotypical individuals who are low-performing in mathematical tasks as well as in individuals with special educational needs, such as dyslexia and autism. This is the first series of studies and meta-analyses to investigate whether elevated levels of atypical handedness are also to be found in individuals with Mathematical Learning Difficulties (MLD). Method: We report three new studies (N= 134; N= 1,899; N= 149) and two sets of meta-analyses (22 studies; N= 3,649) on the handedness rates of MLD and Typically Achieving (TA) individuals. Results: No evidence of a difference in atypical handedness was found when the direction of hand preference was used as the handedness measure, with the exception of weak evidence when writing hand was used as the handedness criterion. When combining data meta-analytically no hand preference differences between the MLD and TA were detected. Conclusions: There is very limited evidence for elevated levels of atypical hand preference in MLD. We suggest that:(i) potential handedness effects are subtle and require larger samples,(ii) direction of hand preference is not a sensitive enough measure of handedness, or that (iii) increased rates of atypical hand preference are related specifically to conditions that present with language difficulties, as handedness is a behavioral index for language lateralization, and not to conditions requiring special educational needs at large. Future studies need to investigate the possible relationship of hand skill and of degree of hand preference with MLD.