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Abstract Behavioral problems are common in children with tuberous sclerosis complex (TSC) and can be challenging to manage at home. Standardized measures were used to assess behavior in 99 pediatric patients with TSC and to evaluate parenting stress in their parents. About 40% of the pediatric patients presented clinically significant behavioral problems, most frequently involving symptoms of autism spectrum disorder, inattention, and hyperactivity. Higher seizure frequency, mixed seizure disorder, and low intellectual functioning placed the patient at significant risk for behavior problems. Almost 50% of participating parents reported experiencing clinically significant parenting stress, which was associated with specific characteristics of the child, including the presence of current seizures, a history of psychiatric diagnosis, low intelligence, and behavioral problems. Clinicians should be aware that behavioral problems are prominent in children with TSC. Referrals for behavioral intervention and monitoring of parental stress should be included in the medical management of children with TSC.