Another high-tempo performance in defence and in attack ripped Italian resistance to shreds as England ran in seven tries to emphasise the strides they have made in the campaign.
Mike Brown's outstanding championship continued with his brace of tries decorating a fine individual contribution, while Owen Farrell, Jack Nowell, Mako Vunipola, Manu Tuilagi and Chris Robshaw also crossed.
It marked a fourth successive victory for the Red Rose since losing 26-24 in France on the opening day and Lancaster said: "We've made huge progress. We played this game last year and won 18-11 with six penalties.
"Today we scored some great tries and we've come here and scored 50, and not many teams have done that, in fact very, very few. So you've got to be proud of the boys really.
"We have produced a big scoreline on the back of a Sunday game against Wales - opponents who emotionally and physically took a lot out of the players - with a team that has an average age of 24. We are in good shape going forward, particularly with quality additions to come back into our squad who we know already are on their way back."
Tuilagi made his first England appearance in a year after completing his comeback from chest surgery, replacing Luther Burrell at outside centre with half an hour to go, and made inroads into a tiring Italy defence.
However, the substitution drew criticism from former World Cup-winning head coach, Sir Clive Woodward, who felt Lancaster's habitual ploy of emptying the bench had robbed the visitors of momentum as they attempted to overturn a points difference deficit to Ireland.
But Lancaster said: "I'm curious as to which substitute didn't add. Manu added. We make our decisions on what we're seeing. And Manu made a great impact when he came on. He scored a try, broke tackles, didn't make any defensive errors, turned the ball over in the last play which resulted in a try. He added value."
A cagey opening saw Italy dominate possession and draw first blood with a long-range penalty from Luciano Orquera that was greeted with a mighty roar from the sell-out 80,000 crowd.
Farrell, who was again out- standing with the boot, levelled the score with a penalty and the Red Rose went on the offensive. A brilliant off-load from Luther Burrell pierced Italy's defence with the Northampton centre's pass out of a tackle by Gonzalo Garcia finding man-of-the-match Brown, who switched on the afterburners and raced over.
Loosehead Mako Vunipola was penalised at a scrum and Orquera obliged with the three points to keep Italy in touch.
Burrell and Danny Care strung together some eye-catching attacks and one of these led to the scrum-half darting across the field for Farrell to go in under the posts.
The floodgates were already opening and this time Farrell was the provider as he rode a tackle and expertly slipped a pass to Brown who galloped over.
Italy's problems mounted in the second half when Marco Bortolami was sin-binned for off-side and soon after their whitewash was breached for a fourth time, Nowell rounding off a backs move at a scrum.
Italy's defence was falling to pieces and they effectively waved England through for their next two tries with Vunipola and Tuilagi strolling over.
It was then the visitors' turn to blunder, however, with wing Leonardo Sarto picking off an intercept try from Joe Launchbury's pass.
There was still time for England to have the final say, though, when captain Chris Robshaw went over in injury-time.
Italy: McLean, Esposito, Campagnaro, Garcia (Massi 73), Sarto, Orquera (Allan 44), Tebaldi, Aguero (Rizzo 47), Ghiraldini, Cittadini (De Marchi 47), Geldenhuys, Bortolami, Furno (Derbyshire 56), Barbieri, Parisse, Derbyshire (Biagi 61). Subs not used: Giazzon, Gori.
Sin-bin: Bortolami (51).
England: Brown, Nowell, Burrell (Tuliagi 54), Twelvetrees (Ford 71), May, Farrell, Care (Dickson 67), M Vunipola (Mullan 76), Hartley (T Youngs 54), Wilson (Thomas 71), Launchbury (Attwood 71), Lawes, Wood (Johnson 67), Robshaw, Morgan.
Referee: Pascal Gauzere (France).