Human and natural activities release Many pollutants in the marine environment. The mixture of pollutants can affect many organisms concurrently. We used Paracentrotus lividus as a model to analyze the effects on signal transduction pathways and stress gene expression in embryos exposed continuously to double stress, cadmium (Cd) from fertilization and UVB at cleavage (Cd/UVB-embryos). Microscopical inspection, we evaluated embryonic morphology after 72 h of development, Tissue-specific markers Were used to assess meSoderm differentiation by immunofluorescence. We analyzed p38MAPK, ERK1/2, and JNK activation by Western blot and mRNA profiles of Pl-MT, Pl-14-3-3epsilon, and Pl-jun genes:by real-time quantitative polymerase chain reaction (qPCR) and the localization of their transcripts by whole mount in,situ hybridization, (WMISH). We found that the Cd/UVB-combined exposure induced morphological malformations in 76% of pluteus embryos, mainly affecting the development of the skeleton, including the normal branching of skeletal roads. In Cd/UVB-embryos, p38MAPK was activated 1 h after UVB exposure and a remarkable overexpression of the Pl-MT, Pl-14.3.3epsilon, and Pl-jun genes 24 h after UVB exposure. Pl-MT and Pl-14.3.3epsilon mRNAs were misexpresed as they were localized in a position different from that observed in wild-type embryos, Le, the intestine. On the contrary,. Pl-jun mRNA has remained localized in the skeletogenic cells despite their displacement in exposed embryos. In conclusion, Cd/UVB exposure affected skeletal patterning producing alternative morphologies in which p38MAPK activation and Pl-MT, Pl-14.-3.3epsilon, and Pl-jun gene overexpression seem linked:to a protective role against the stress response induced by Cd/UVB.