How micro is laser microdissection? This study compared the spatial resolution of laser microdissection achieved by two laser systems: the ArF excimer laser which is strongly absorbed by tissue protein, and the Er:YAG laser which is strongly absorbed by tissue water. Both lasers penetrate tissue only a couple microns and are suitable for laser microdissection, and in this report the lasers ablated the outer dead-cell layer of the skin called the stratum corneum. The study involved dorsal skin sites on 8 rats for the ArF excimer and 10 rats for the Er:YAG. Ag/AgCl-gel electrodes were used to measure the passive DC resistance (R) and the active DC voltage (V) of skin sites which had received increasing numbers of ablative laser pulses (9 mJ/pulse, Er:YAG; 48 mJ/pulse, ArF excimer). About 8 pulses were required before a sudden drop in Ra and a sudden rise in V was observed. The R dropped from 4 ± 0.2 (18) Mohm down to 1.5 ± 0.2 (18) Mohm; mean ± standard deviation (number of skin sites). The V was initially -56 ± 5 mV, then dropped to -3 ± 0.4 mV after laser ablation penetrated and destroyed the battery. The Er:YAG laser required 8.3 ± 1.5 pulses to achieve 50% of the full change in R and V; the ArF excimer laser required 76 ± 2 pulses. The changes in R and V per depth of tissue ablated were identical for the two lasers, despite their distinct differences in absorbing chromophore and efficiency of ablation.