To improve current ALCL research models using artificial overexpression of NPM-ALK, we developed a CRISPR/Cas-based model which selectively introduces syntenic Npm-Alk translocations in a murine model cell line, leading to faithful Npm-Alk expression from the endogenous promoter and a more accurate recapitulation of the disease phenotype. This evidence concerns the gene NPM1 and anaplastic large cell lymphoma.