No studies to date have explored the correlates of insistence on sameness (IS) in individuals with germline pathogenic mutations in PTEN. This study aimed to characterize the relationship between IS and executive functioning (EF) and anxiety as well as with age, sex and Full-Scale IQ (FSIQ) among individuals with PTEN mutations. The sample included 38 individuals with PTEN mutation and ASD diagnosis (PTEN-ASD; n = 38; M(age)= 8.93 years, SD(age)= 4.75), 25 with ASD and macrocephaly but with no PTEN mutation (Macro-ASD; M(age)= 11.99 years; SD(age)= 5.15) and 23 with PTEN mutation without ASD (PTEN-no ASD; M(age)= 8.94 years; SD(age)= 4.85). The Repetitive Behavior Scale-Revised (RBS-R), the Child Behavior Checklist (CBCL), and the Behavior Rating Inventory of Executive Function (BRIEF) were used as measures of IS, anxiety, and Inhibitory Control, Set-shifting and Working Memory EF domains, respectively. FSIQ was also available. IS was significantly associated with FSIQ (r= −.36, p= .002), CBCL anxiety (r= .45, p< .001), BRIEF Inhibitory Control (r= .36, p= .002),Set-Shifting (r= .65, p< .001) and Working Memory (r= .27, p= .023) T scores. The final hierarchical regression model accounted for 44.2% of the variance in IS, with Set-Shifting as a unique independent predictor of IS score (t = 4.30, p< .001). This investigation furthers our understanding of IS by providing the first preliminary evidence for the EF—anxiety—IS interrelationship in individuals with PTEN mutations and with macrocephalic ASD.