Lettuce crop is an important horticultural crop of several Mediterranean countries, including Italy. The Italian region which is a major producer of lettuce crops is Apulia, where this crop is cultivated in open fields an in greenhouses. Since several microbial pathogens are responsible for important diseases found on lettuce produced in greenhouses, in this study, the experimental activities focused on the most severe fungal soilborne pathogens, i.e.,Sclerotinia sclerotiorumandAthelia rolfsii. Their control is often performed with fungicides which cause public concern over the environment and human health. The main aims of this study were to determine the biocontrol efficacy of aStreptomycesstrain in vitro and in vivo conditions on lettuce seedlings againstAthelia rolfsiiandSclerotinia sclerotiorumas severe fungal soilborne pathogens through the application of its vegetative propagules and putative bioactive crude extracts via filtrate culture. The results obtained confirm a significant effectiveness of CARA17 strain to control the severity of both fungal soilborne pathogens during two different experiments: when it is used as vegetative propagules and as a culture filtrate containing putative bioactive metabolites in vitro and in vivo conditions. These preliminary results demonstrated that the actinomycetes CARA17 strain is valid as a biocontrol agent (BCA) against both the severe phytopathogens used in this study. The biocontrol action performed from the CARA17 strain is clearly and mainly due to the putative bioactive crude extracts produced, but further studies are necessary to identify which metabolites (polyphenols, terpenes, fatty acids, etc.) are produced from thisStreptomycesstrain.