Green nail syndrome (GNS) is a persistent greenish pigmentation of the nail plate, originally described in 1944 by Goldman and Fox, due to <i>Pseudomonas aeruginosa</i> infection. Recently, pulmonary co-infection of <i>P. aeruginosa</i> and <i>Achromobacter</i> spp. has been described in patients with cystic fibrosis. <i>Achromobacter xylosoxidans</i> is a multidrug-resistant (MDR) pathogen involved in lung and soft tissue skin infections. Both <i>Achromobacter xylosoxidans</i> and <i>P. aeruginosa</i> are mainly found in humid environments or in water. There are no recognized co-infections due to <i>P. aeruginosa</i> and <i>A. xylosoxidans</i> in the skin and appendages. We describe two cases of GNS, the first due to <i>P. aeruginosa</i> associated with <i>Achromobacter xylosoxidans</i>; the other due to MDR <i>P. aeruginosa</i>, both successfully treated with topical ozenoxacin 1% cream daily for 12 weeks. The clinical management of GNS can be confusing, especially when the bacterial culture result is inconsistent or when non-<i>Pseudomonas</i> bacteria are isolated. In our case, due to the co-infection of <i>P. aeruginosa</i> and <i>Achromobacter</i> spp., local treatment with ozenoxacin – the first nonfluorinated quinolone – could be a safe and effective treatment in case of MDR nail infections. Further studies are required to evaluate clinical isolation from nail infections and the co-presence of <i>P. aeruginosa</i> and <i>A. xylosoxidans</i>.