in Wiley Online Library (wileyonlinelibrary.com).In an attempt to improve anticancer activity, a series of retinoids-chromene hybrids was described. The novel heterocyclic chromene-retinoids hybrid including oxygen as a heteroatom in a six-membered cyclic ring (2H-chromene or 2H-1-benzopyran) was designed and synthesized by introducing different groups such as an aromatic or styrylphenyl ring in 6-position of 2H-chromene. These novel compounds were synthesized by using the efficient cascades one-pot process involving Wittig-Horner-Emmons reaction and Suzuki-Miyaura cross-coupling pallado-catalyzed reactions with 60% to 90% overall yields. These new compounds were tested against glioblastoma multiforme brain cancer, medulloblastoma, neuroblastoma cell lines, and breast cancer MCF-7 cell lines. Two of them exhibited an appreciable anti-tumor activity in the low micromolar range, which opens new perspectives for therapeutic application on humans.