Neuroblastoma (NB) is a malignant tumor deriving from the neural crest that is responsible for 13% of cancer‐related deaths in children. Phosphoinositide 3‐kinases (PI3Ks) play a central role in NB tumorigenesis. PI3Ks activate AKT, which regulates survival and stabilizes the MYCN oncogene. Both MYCN and AKT are markers for poor prognosis in NBs. Inhibiting PI3Ks with pan‐inhibitors blocks malignant progression in vivo. These inhibitors have high toxicity that limits their use in NB treatment. Though there are three classes of PI3Ks, only Class I has been implicated in NB. Class 2 beta PI3K (PI3KC2β) is overexpressed in cancer and involved in adherent and anchorage‐independent growth of cancer cells. We found that the scaffold protein intersectin 1 (ITSN1) interacts with PI3KC2β and regulates its activation and Akt activation in mouse NB lines. Thus, we examined the role of the ITSN1‐PI3KC2β pathway in human NB tumorigenesis. We found that stable silencing of ITSN1 in human NB cells attenuates their growth both in soft agar assays in vitro and in xenograft tumor assays in vivo. Furthermore, PI3KC2β overexpression restores anchorage‐independent growth of ITSN1‐depleted NB cells suggesting that PI3KC2β mediates ITSN1's tumorigenic phenotype. This study reveals a new pathway, i.e., ITSN1‐ PI3KC2β is involved in regulating the pathogenesis of NBs.