Background Although its incidence has been decreasing during the last decade, malaria is still a major public health issue in Madagascar. The use of Long Lasting Insecticidal Nets (LLIN) remains a key malaria control intervention strategy in Madagascar, however, it encounters some obstacles. The present study aimed to explore the local terminology related to malaria, information channels about malaria, attitude towards bed nets, and health care seeking practices in case of fever. This article presents novel qualitative findings about malaria. Until now, no such data has been published for Madagascar. Methods A comparative qualitative study was carried out at four sites in Madagascar, each differing by malaria epidemiology and socio-cultural background of the populations. Seventy-one semi-structured interviews were conducted with biomedical and traditional caregivers, and members of the local population. In addition, observations of the living conditions and the uses of bed net were conducted. Results Due to the differences between local and biomedical perspectives on malaria, official messages did not have the expected impact on population in terms of prevention and care seeking behaviors. Rather, most information retained about malaria was spread through informal information circulation channels. Most interviewees perceived malaria as a disease that is simple to treat. Tazomoka (“mosquito fever”), the Malagasy biomedical word for malaria, was not used by populations. Tazo (“fever”) and tazomahery (“strong fever”) were the terms more commonly used by members of the local population to refer to malaria related symptoms. According to local perceptions in all areas, tazo and tazomahery were not caused by mosquitos. Each of these symptoms required specific health recourse. The usual fever management strategies consisted of self-medication or recourse to traditional and biomedical caregivers. Usage of bed nets was intermittent and was not directly linked to protection against malaria in the eyes of most Malagasy people. Conclusions This article highlights the conflicting understanding of malaria between local perceptions and the biomedical establishment in Madagascar. Local perceptions of malaria present a holistic vision of the disease that includes various social and cultural dimensions, rather than reflecting one universal understanding, as in the biomedical image. The consideration of this “holistic vision” and other socio-cultural aspects surrounding the understanding of malaria is essential in implementing successful control intervention strategies.