Wild halophytic tomato has long been considered as an ideal gene donor for improving salt tolerance in tomato cultivars. Extensive research has been focused on physiological and QTL characterization of wild tomato species in comparison with cultivated tomato. However, the global gene expression modification of wild tomato in response to salt stress is not well known. A wild tomato genotype, Solanum pimpinellifolium 'PI365967' is significantly more salt-tolerant than a cultivar, Solanum lycopersicum 'moneymaker', as evidenced by its higher survival rate and lower growth inhibition at vegetative stage. Affymetrix Tomato Genome Arrays containing 9200 probe sets was used to compare the transcriptome of PI365967 and Moneymaker. After treatment with 200 mM NaCl for 5 h, PI365967 showed relatively fewer responsive genes compared to Moneymaker. Salt Overly Sensitive (SOS) pathway was found to be more active in PI365967 than in Moneymaker, coinciding with relatively less accumulation of Na+ in shoots of PI365967. A gene encoding salicylic acid-binding protein 2 (SABP2) was induced by salinity only in PI365967, suggesting a possible role of salicylic acid signaling in salt response of PI365967. The fact that two genes encoding lactoylglutathione lyase were salt-inducible only in PI365967, together with much higher basal expression of several glutathione S-transferase genes, suggested a more effective detoxification system in PI365967. The specifically down-regulation in PI365967 of a putative high-affinity nitrate transporter, known as a repressor of lateral root initiation, may explain the better root growth of this genotype during salt stress.