Abstract Context General practitioners (GPs) play a key role in the end-of-life care of patients; however, currently in Italy, there are no national population-based studies available of the knowledge and activities of GPs in palliative care. Objectives This survey aimed to investigate the knowledge, opinions, and activities of Italian GPs regarding palliative care. Methods A telephone survey of 1690 GPs was performed. Information was gathered through an ad hoc questionnaire. Results Valid interviews were obtained for 88% of the sampled GPs ( n = 1489). Regarding knowledge, 25% of GPs recognized a correct definition of palliative care, 41% the objectives of palliative care, 66% that palliative care should be provided by a multiprofessional team including GPs, and 60% that in-home care for patients at the end of life requires an individual plan care. Furthermore, 92% of them reported that “there is no maximum daily morphine dose for the management of pain.” Regarding opinions, most of the GPs strongly agreed that for patients at the end of life, the GPs' duties included availability during working hours to break bad news to patients and families and to collaborate with the multiprofessional team in establishing an individual care plan. Finally, regarding activities, most GPs reported that, in their daily practice with patients at the end of life, they discontinue the drugs that are not beneficial to symptom management and seek advice from palliative care physicians when symptom management is ineffective. Conclusion This survey reveals the uncertainty of GPs regarding many theoretical issues but a strong willingness to integrate with the multiprofessional palliative care team. To further enhance the skills of GPs and facilitate the collaboration with palliative care services, it might be useful to realize ad hoc training schemes tailored to the different organizational procedures of in-home palliative care services.