Rett Syndrome (RTT) is characterized by severe impairment in fine motor (FM) and expressive language (EL) function, making accurate evaluations of development difficult with standardized assessments. In this study, the administration and scoring of the Mullen Scales of Early Learning (MSEL) were adapted to eliminate the confounding effects of FM and EL impairments in assessing development. Forty-seven girls with RTT were assessed with the Adapted-MSEL (MSEL-A), a subset (n = 30) was also assessed using the Vineland Adaptive Behavior Scales-Second Edition (Vineland-II) and a further subset (n = 17) was assessed using an eye-tracking version of the MSEL (MSEL-ET). Participants performed better on the visual reception (VR) and receptive language (RL) domains compared to the FM and EL domains on the MSEL-A. Individual performance on each domain was independent of other domains. Corresponding MSEL-A and Vineland-II domains were significantly correlated. The MSEL-ET was as accurate as the MSEL-A in assessing VR and RL, yet took a 44% less time. Results suggested that the MSEL-A and the MSEL-ET could be viable measures for accurately assessing developmental domains in children with RTT.