Class switch recombination (CSR) in B lymphocytes is initiated by the introduction of multiple DNA double-strand breaks (DSBs) into the switch (S) regions that flank immunoglobulin heavy chain (IgH) constant region exons. CSR is completed by joining a DSB in the Sμ region to a DSB in a downstream S region (e.g. Sγ1) by end-joining. In normal cells, CSR joining is mediated by classical non-homologous end-joining (C-NHEJ), which employs the Ku70/80 complex for break recognition and XRCC4/DNA Lig4 for ligation. C-NHEJ forms junctions either with short nucleotide overlaps referred to as micro-homologies (MH) or no homologies (direct). During CSR, DSBs can also be joined within the same S region to generate intra-switch deletions (ISDs). In addition, S region DSBs can be involved in translocations, which become more frequent in the absence of C-NHEJ factors (e.g. XRCC4). In XRCC4/Lig4-deficient cells, substantial CSR occurs via an "alternative" end-joining pathway (A-EJ) that generates mainly MH-mediated joins. Because upstream C-NHEJ components are still present in XRCC4- or Lig4-deficient B cells, CSR in these cells could still be catalyzed by C-NHEJ, but using a different ligation complex. To address this, we assayed for CSR in B cells deficient for the C-NHEJ initiation factor Ku70 in addition to Lig4, and found that they undergo robust CSR, firmly demonstrating that an A-EJ pathway distinct from C-NHEJ exists for CSR end-joining. In addition, we find that the absence of C-NHEJ greatly increases the frequency of ISDs in both Sμ and Sγ1, suggesting a preference of A-EJ for short-range chromosomal joining. IgH chromosomal translocations to the c-myc oncogene are also increased in the combined absence of Ku70 and Lig4. Together, our results uncover a C-NHEJ-independent A-EJ pathway that mediates both CSR and translocations. To define the A-EJ joining complex, we tested whether the ligase Lig3 and its cofactor XRCC1 are required for CSR and translocations in XRCC4/Lig4-deficient cells. We found that neither Lig3 nor XRCC1 play a major role in A-EJ, based on CSR and chromosomal reporters. Since mammalian cells have only three ligases (Lig1, Lig3 and Lig4), our findings implicate Lig1 as the main A-EJ ligase.