In the Romanian public medical system psychosocial assessment is not integrated into routine oncological treatment and care. According to APSCO research data, cancer distress is recorded in about half of the Romanian cancer inpatients, the maximum admissible level. In this context, creating a clinical practice guide in psycho-oncology is one of the first actions needed to be taken. This guide corroborate clinical experience from within the Romanian oncology system, psychosocial resources available to Romanian professionals in cancer care and best practice recommendations from psycho-oncology literature. The intervention scenarios presented here are consistent with care requirements implied by the oncology hospital system in Romania. The therapeutic act involves three structural stages (initial, intermediate, final) of psycho-oncological intervention, several therapeutic targets and cancer-specific intervention techniques being presented in detail for each stage. A number of best practices for doctor-patient communication and psycho-oncological intervention, as well as recommendations for a comprehensive care taking into account the patients’ needs in order to maintain continuity and quality of life during hospitalization and rehabilitation have resulted from this line of action.