While characterizing macrolide and lincosamide resistance mechanisms in a subset of Canadian Nosocomial Infection Surveillance Program (CNISP) methicillin-resistant Staphylococcus aureus (MRSA) isolates (monitored since 1995), we identified two isolates carrying ermA yet susceptible to erythromycin and clindamycin. A retrospective examination of susceptibility and molecular typing data (1995–2007) found 13 SCCmec II MRSA isolates belonging to CMRSA2 (USA100) and spa type 2 (TJMBMDMGMK) from three Canadian provinces (British Columbia, Manitoba, Ontario), which were susceptible to erythromycin (MIC 0.25 g/ml) and clindamycin (MIC 0.5 g/ml). PCR confirmed the presence of the ermA coding sequence, but amplification with primers spanning a 196-bp upstream region and the entire coding sequence yielded smaller amplicons from genomic DNA and reverse-transcribed cDNA. DNA sequence analysis revealed a 48-bp deletion (nucleotides 5,277 to 5,324) in Tn554 (GenBank accession no. X03216) in these isolates. The ermA translation attenuation sequence comprises at least a 19-mer peptide coding sequence and two pairs of inverted repeats (IR1/IR2 and IR3/IR4) upstream of the ErmA AUG start codon; in the absence of inducers, ermA mRNA forms stable hairpins that sequester the Shine-Dalgarno sequence and start codon, while inducing macrolides bind and stall ribosomes during 19-mer translation, leading to IR2/IR3 hairpin formation and liberation of translation initiation elements. The 48-bp deletion removed these translation initiation elements, preventing ErmA protein production. Contrary to previous reports of ermA alterations causing constitutive erythromycin resistance, this deletion represents a novel event conferring an erythromycin- and clindamycin-susceptible phenotype. Ongoing monitoring is needed to determine the frequency of this deletion over time.