Introduction For assessment of lower extremity swelling using lymphoscintigraphy, several nuclear medicine departments in the UK have recently switched from 99mTc-Nanocoll to 99mTc-Nanoscan. The aim of the study was to compare quantitative and semiquantitative features of lymphoscintigraphy between these two tracers. Methods Twenty patients received 99mTc-Nanocoll and 20 received 99mTc-Nanoscan either side of the switch-over in our department. Tracers were compared with respect to visualisation of the liver, para-aortic lymph nodes and urine (all graded by consensus from 0 to 3; invisible-to-very prominent); and with respect to ilio-inguinal nodal quantification and ratio of liver-to-summed bilateral ilio-inguinal nodal activity at 120 min postinjection (L/N120). Scans were deemed abnormal when there was lymph diversion through skin or deep system, no activity in ilio-inguinal nodes at 60 min or negligible ilio-inguinal activity (<5%, left plus right) at 120 min. Results Liver was visualised in 18/20 99mTc-Nanocoll but only 3/20 99mTc-Nanoscan scans. Moreover, para-aortic activity was less prominent after 99mTc-Nanoscan. Urinary activity was more prominent after 99mTc-Nanocoll. There were 9/20 patients with stomach activity after 99mTc-Nanocoll compared with 1/20 after 99mTc-Nanoscan. Urinary and stomach activities correlated. There was an elevated L/N120, and therefore a suspicion of peripheral lympho-venous communication, in the single 99mTc-Nanoscan patient who displayed prominent hepatic activity. Conclusion Hepatic activity is the result of accumulation of colloidal degradation products generated in lymph nodes, rather than intact colloid. 99mTc-Nanoscan gives less hepatic activity than 99mTc-Nanocoll because it is more resistant to intranodal degradation. Peripheral lymphovenous communication remains a possible alternative route for activity to reach the liver.