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<i>Listeria monocytogenes</i> (<i>Lm</i>) is the causative agent of human listeriosis. <i>Lm</i> strains have different virulence potential. For this reason, we preliminarily characterised via Whole-Genome Sequencing (WGS) some <i>Lm</i> strains for their key genomic features and virulence-associated determinants, assigning the clonal complex (CC). Moreover, the ability of the same strains to adhere to and invade human colon carcinoma cell line Caco-2, evaluating the possible correspondence with their genetic virulence profile, was also assessed. The clinical strains typed belonged to clonal complex (CC)1, CC31, and CC101 and showed a very low invasiveness. The <i>Lm</i> strains isolated from food were assigned to CC1, CC7, CC9, and CC121. All CC1 carried the hypervirulence pathogenicity island LIPI-3 in addition to LIPI-1. Premature stop codons in the <i>inlA</i> gene were found only in <i>Lm</i> of food origin belonging to CC9 and CC121. The presence of <i>LIPI2_inlII</i> was observed in all the CCs except CC1. The CC7 strain, belonging to an epidemic cluster, also carried the internalin genes <i>inlG</i> and <i>inlL</i> and showed the highest level of invasion. In contrast, the human CC31 strain lacked the <i>lapB</i> and <i>vip</i> genes and presented the lowest level of invasiveness. In <i>Lm</i>, the genetic determinants of hypo- or hypervirulence are not necessarily predictive of a cell adhesion and/or invasion ability in vitro. Moreover, since listeriosis results from the interplay between host and virulence features of the pathogen, even hypovirulent clones are able to cause infection in immunocompromised people.