Plasmid-mediated class C beta-lactamases are reported from Enterobacteriaceae with increasing frequency. They likely originate from chromosomal AmpC of certain Gram-negative bacterial species and subsequently are mobilized onto transmissible plasmids. There are reports of unfavorable clinical outcomes in patients infected with these organisms and treated with broad-spectrum cephalosporins. However, unlike class A extended-spectrum beta-lactamases (ESBLs), no screening and confirmatory tests have been uniformly established for strains that produce class C beta-lactamases. Reduced susceptibility to cefoxitin is a sensitive but not specific indicator of class C beta-lactamase production. Simple confirmatory tests including tests using boronic acid compounds as specific class C beta-lactamase inhibitors have recently been developed. Their utilization will enable clinical microbiology laboratories to report those strains producing plasmid-mediated class C beta-lactamases as being resistant to all broad-spectrum cephalosporins, thus allowing physicians to prescribe appropriate antimicrobial therapy.