Despite the immense ecological, biogeochemical and paleontological/paleoecological importance of living and fossil coccolithophores, fundamental gaps exist in the biological knowledge of this group of marine protists. The traditional approach of examining the morphology of their beautiful skeletons to study their ecology and evolution has important limitations. Simple questions, such as: When did the coccolithophores first appear? How many species exist in the contemporary ocean, and existed in past oceans? What are the phylogenetic links between these species and between the lineages to which they belong? What is their life-cycle, and are they autotrophic or heterotrophic organisms? Are still poorly understood due to a paucity of information on their genotypic and phenotypic (other than the coccoliths) characters? Analysis of mutations within the DNA of coccolithophores using population genetics, phylogenetic, and genomic approaches may help to answer these questions. Here we synthesize the first conclusions resulting from the still very limited number of molecular studies on coccolithophores and emphasize some of the most important questions that have consequently arisen. We finally propose new approaches using combined optic and genetic techniques to explore the ecology and evolution of coccolithophores at the boundary between molecular biology, oceanography, and paleontology.