My first serious system-related problem. It happens in Synaptic Package Manager and Ubuntu software center also crashes.
The directory exists.
E: Read error - read (21: Is a directory)
E: Problem opening /var/lib/apt/lists/Ubuntu%2010.04%20LTS%20%5fLucid%20Lynx%5f%20-%20Release%20i386%20(20100429)_dists_lucid_restric ted_binary-i386_Packages
E: The package lists or status file could not be parsed or opened.
E: _cache->open() failed, please report.